Primary Outcomes

Description: An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Measure: Number of Participants with Adverse Events

Time: Up to 24 Months

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Description: The RPTD of ABBV-399 when administered as monotherapy and in combination with osimertinib, erlotinib or nivolumab will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data.

Measure: Recommended Phase 2 Dose (RPTD) of ABBV-399 when Administered as Monotherapy and in Combination with Osimertinib, Erlotinib or Nivolumab

Time: Up to 24 Months

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Description: AUC (0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to the time of the last measurable concentration.

Measure: Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t)

Time: Up to 24 months

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Description: Maximum observed plasma concentration (Cmax).

Measure: Maximum observed plasma concentration (Cmax)

Time: Up to 24 months

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Description: Time to Cmax (Tmax).

Measure: Time to Cmax (Tmax)

Time: Up to 24 months

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Description: Terminal elimination half life.

Measure: Terminal elimination half life

Time: Up to 24 months

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Primary Outcomes

Description: Survival estimates will include death from any cause.

Measure: Overall Survival

Time: From date of randomization through study completion, up to 10 years

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Secondary Outcomes

Description: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Lung Cancer (LC 13) survey instruments will assess patients' general state of physical, social/family, emotional and functional well-being.

Measure: Patient reported health-related quality of life

Time: 5 years

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Description: The St George's Respiratory Questionnaire will evaluate respiratory symptoms, activity limitations from breathlessness, and impact of respiratory function on social and psychological functioning.

Measure: Respiratory Symptoms

Time: 5 years

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Description: The EQ-5D-5L (EuroQOL-5D) survey will measure quality adjusted life years.

Measure: Health State Utilities

Time: 5 years

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Description: Cause of death will be determined by an independent adjudication committee.

Measure: Lung cancer mortality

Time: From date of randomization until date of death from any cause, assessed up to 10 years.

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Description: Post-treatment surveillance imaging will evaluate patients every 6 months for local, regional, and/or distant disease control.

Measure: Tumor patterns of failure

Time: 5 years

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Description: The Forced Expiratory Volume at 1 second (FEV1) will evaluate an objective measure of breathing function.

Measure: Respiratory Function

Time: 5 years

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Primary Outcomes

Description: Complete Response (CR) Disappearance or fibrosis of all target lesions. Any pathologic lymph nodes must have reduction in short axis to <10mm and standardized uptake value (SUV) is <4. Partial Response (PR) At least 30% decrease in sum of longest diameters of target lesions (compared to initial on study baseline) and any decrease in SUV in Fludeoxyglucose 18F (18FDG) imaging Stable disease (SD) 0-29% decrease in sum of longest diameters of target lesions (compared to initial on study baseline) or 0-19% increase in sum of longest diameters of target lesions (compared to initial on study baseline). SUV may increase or decrease Progressive disease 20% or more increase of sum of longest diameters of target lesions (compared to initial on study baseline). The sum must also be at an increase of at least 5mm or one or more new lesions that are considered metastatic disease

Measure: Tumor response according to RECIST Criteria

Time: Up to 1 Year

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Secondary Outcomes

Description: Average time from beginning of treatment to progression, death, or one year, whichever comes first. An underlying clinical benefit rate of 25% would indicate that ONC201 has a therapeutic effect, whereas an underlying rate <5% would indicate a lack of activity

Measure: Average duration of lack of progression: Clinical response

Time: Up to 1 Year

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Description: time from beginning of treatment until death, or one year, whichever comes first.

Measure: Overall survival

Time: Up to 1 Year

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Description: to achieve this secondary endpoint of anti-hypertensive medication reduction in PC-PG subjects (N=12) data at 3 months will be required. An underlying clinical benefit rate of 25% would indicate that ONC201 has a therapeutic effect, whereas an underlying rate <5% would indicate a lack of activity

Measure: Average change in anti-hypertensive medication

Time: from beginning of treatment to 3 months

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Primary Outcomes

Measure: Phase 1: Number of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs)

Time: Up to 48 months

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Description: Severity grade will be evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which will be assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.

Measure: Phase 1: Number of Participants Based on Severity of TEAEs

Time: Up to 48 months

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Measure: Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

Time: Up to Cycle 1 (Cycle length is equal to [=] 21 days)

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Measure: Phase 1: Number of Participants With Clinically Significant Laboratory Values

Time: Up to 48 months

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Description: ORR is defined as percentage of participants who achieve complete response (CR) and partial response (PR), as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) for participants with solid tumors or Lugano classification for lymphoma.

Measure: Phase 2: Overall Response Rate (ORR)

Time: From the first dose until best response is achieved (up to 4 years)

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Measure: COVID-19 Expansion: Number of Participants With Greater Than or Equal to (>=) 2 log Reduction From Baseline in Viral Load or Below Level of Detection (Negative) in Nasopharyngeal or Oropharyngeal Samples

Time: Up to 9 months

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Secondary Outcomes

Measure: Phase 2: Number of Participants Reporting one or More TEAEs

Time: Up to 48 months

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Description: Severity grade will be evaluated as per the NCI CTCAE Version 5.0, except for CRS, which will be assessed by ASTCT consensus grading criteria.

Measure: Phase 2: Number of Participants Based on Severity of TEAEs

Time: Up to 48 months

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Measure: Phase 2, Cmax: Maximum Observed Plasma Concentration for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length is equal to [=] 21 days)

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Measure: Phase 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Measure: Phase 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Measure: Phase 2, AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Measure: Phase 2, Terminal Disposition Phase Half-life (t1/2z) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Measure: Phase 2, Total Clearance (CL) After Intravenous Administration for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Measure: Phase 2, Volume of Distribution at Steady State After Intravenous Administration (Vss) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Description: ORR is defined as percentage of participants who achieve CR and PR through the study (approximately 4 years), as determined by the investigator according to the RECIST V1.1 for participants with solid tumors or Lugano classification for lymphoma.

Measure: Phase 2: ORR

Time: From the first dose until best response is achieved (up to 4 years)

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Description: DOR is the time from the date of first documentation of a PR or better to the date of first documentation of progressive disease for responders (PR or better) and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.

Measure: Phase 2: Duration of Response (DOR)

Time: From the time of documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study (up to 4 years)

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Description: DCR is defined as the percentage of participants who achieve stable disease (SD) or better (determined by the investigator according to RECIST v1.1 criteria for solid tumors or Lugano classification for lymphoma) greater than (>) 6 weeks during the study in the response-evaluable population.

Measure: Phase 2: Disease Control Rate (DCR)

Time: From the first dose until best response is achieved (up to 4 years)

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Description: TTR is defined as the time from the date of first study drug administration to the date of first documented PR or better by the investigator for responders according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.

Measure: Phase 2: Time to Response (TTR)

Time: From the date of first study drug administration to the date of first documented PR or better (up to 4 years)

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Description: TTP is defined as the time from the date of the first dose administration to the date of first documented progressive disease and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.

Measure: Phase 2: Time to Progression (TTP)

Time: From the date of first study drug administration to the date of first documented PD (up to 4 years)

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Description: PFS is defined as the time from the date of the first dose administration to the date of first documentation of progressive disease or death due to any cause, whichever occurs first and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.

Measure: Phase 2: Progression-free Survival (PFS)

Time: From the date of the first dose administration to the date of first documentation of PD or death due to any cause whichever occurs first, through the end of the study (up to 4 years)

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Description: OS is defined as the time from the date of the first dose administration to the date of death.

Measure: Phase 2: Overall Survival (OS)

Time: From the date of first study drug administration to the date of death (up to 4 years)

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Measure: Phase 2: Number of Participants With TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation and SUMO Pathway Inhibition in Skin/Blood

Time: Up to 48 months

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Measure: COVID-19 Expansion: Number of Participants Reporting one or More TEAEs

Time: Up to 9 months

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Description: Severity Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 5.0.

Measure: COVID-19 Expansion: Number of Participants Based on Severity of TEAEs

Time: Up to 9 months

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Measure: COVID-19 Expansion: Duration of TEAEs

Time: Up to 9 months

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Description: NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.

Measure: COVID-19 Expansion: Change from Baseline in National Early Warning Score (NEWS)

Time: Up to 9 months

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Description: Percentage of participants will be reported based on severity rating on a 6-point ordinal scale, which will include: 1 (death); 2 (hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation, hospitalized); 3 (on non-invasive ventilation or high flow oxygen devices); 4 (hospitalized, requiring supplemental oxygen); 5 (hospitalized, not requiring supplemental oxygen); and 6 (not hospitalized).

Measure: COVID-19 Expansion: Percentage of Participants Reporting Each Hospitalization Severity Rating

Time: Up to 9 months

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Description: Change from Baseline in SARS-CoV-2 viral Load in nasopharyngeal or oropharyngeal samples will be determined by viral response. The nasopharyngeal swab will be collected from both nostrils or from the same nostril every time.

Measure: COVID-19 Expansion: Change From Baseline in SARS-CoV-2 Viral Load in Nasopharyngeal or Oropharyngeal Samples

Time: Up to 9 months

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Measure: COVID-19 Expansion: Percentage of Participants Requiring Oxygen Supplementation; Assisted or Positive Pressure Non-invasive Ventilation; and Invasive Ventilation, on Days 3, 5, 8, 11, 15, and 30

Time: Days 3, 5, 8, 11, 15, and 30

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Measure: COVID-19 Expansion: Percentage of Participants That met Intensive Care Unit (ICU) Criteria

Time: Up to 9 months

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Measure: COVID-19 Expansion: Duration of Hospitalization

Time: Up to 9 months

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Description: Time from the first dose of TAK-981 to viral load negativity (below level of detection).

Measure: COVID-19 Expansion: Time to Viral Ribonucleic Acid (RNA) Negativity in Nasopharyngeal or Oropharyngeal Samples

Time: Up to 9 months

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Description: Time from first dose of TAK-981 to participant's discharge or to NEWS score <=3. NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.

Measure: COVID-19 Expansion: Time to Discharge or to a NEWS of Less Than or Equal to (<=) 3 and Maintained for 24 Hours

Time: Up to 9 months

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Measure: COVID-19 Expansion: Number of Deaths in Hospital due to any Cause in First 30 Days and in 90 Days

Time: Days 30 and 90

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Primary Outcomes

Description: DLTs will be evaluated during the first cycle. The number of DLTs will be used to determine the maximum tolerated dose (MTD)

Measure: Number of participants with dose limiting toxicities (DLTs)

Time: Baseline through day 28

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Description: Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy

Measure: Number of participants with treatment emergent adverse events (AEs)

Time: Baseline through up to 2 years or until disease progression

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Description: Laboratory abnormalities as characterized by type, frequency, severity, and timing.

Measure: Number of participants with laboratory abnormalities

Time: Baseline through up to 2 years or until disease progression

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Description: Best Overall Response by RECIST 1.1

Measure: Objective Response Rate

Time: Baseline through up to 2 years or until disease progression

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Secondary Outcomes

Description: Single dose PK will be calculated including Maximum Observed Plasma Concentration (Cmax).

Measure: Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including Time to reach Maximum Observed Plasma Concentration (Tmax).

Measure: Pharmacokinetic Parameters: Time to reach Maximum Observed Plasma Concentration (Tmax)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast)

Measure: Pharmacokinetic Parameters: Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including, as data permit, terminal elimination half life (t1/2)

Measure: Pharmacokinetic Parameters: Terminal elimination half life (t1/2)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including, as data permit, Area Under the Curve from time 0 extrapolated to infinity (AUCinf)

Measure: Pharmacokinetic Parameters: AUC from time 0 extrapolated to infinity (AUCinf)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including, as data permit, apparent oral plasma clearance (CL/F)

Measure: Pharmacokinetic Parameters: Apparent oral plasma clearance (CL/F)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including, as data permit, apparent volume of distribution (Vz/F)

Measure: Pharmacokinetic Parameters: Apparent volume of distribution (Vz/F)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including Maximum Observed Steady State Plasma Concentration (Css,max).

Measure: Pharmacokinetic Parameters: Maximum Observed Steady State Plasma Concentration (Css,max)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max).

Measure: Pharmacokinetic Parameters: Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including Area Under the Curve within one dose interval (AUCss,t)

Measure: Pharmacokinetic Parameters: Area Under the Curve within one dose interval (AUCss,t)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including, as data permit, steady state apparent oral plasma clearance (CL/F)

Measure: Pharmacokinetic Parameters: Steady state apparent oral plasma clearance (CL/F)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8. 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including, as data permit, steady state apparent volume of distribution (Vss/F)

Measure: Pharmacokinetic Parameters: Steady state apparent volume of distribution (Vss/F)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including, as data permit, accumulation ratio (Rac)

Measure: Pharmacokinetic Parameters: Accumulation ratio (Rac)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: DOR as assessed using RECIST 1.1

Measure: Duration of response (DOR)

Time: Baseline through up to 2 years or until disease progression

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Description: PFS as assessed using RECIST 1.1.

Measure: Progression free survival (PFS)

Time: Baseline through up to 2 years or until disease progression

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Description: TTP as assessed using RECIST 1.1.

Measure: Time to progression (TTP)

Time: Baseline through up to 2 years or until disease progression

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Description: Proportion of participants alive at 6 months, 1 year and 2 years.

Measure: Overall Survival (OS)

Time: Baseline through up to 2 years

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Primary Outcomes

Description: The occurrence of DLTs will be used to establish the maximum tolerated dose (MTD) of MEDI5395.

Measure: Number of subjects with adverse events (AEs) serious adverse events (SAEs) and dose limiting toxicities (DLTs).

Time: From the time of informed consent until 90 days after the last dose of investigational product (MEDI5395 or durvalumab)

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Secondary Outcomes

Description: The ORR is defined as the proportion of subjects with confirmed response (CR) or confirmed partial response (PR).

Measure: Objective response rate (ORR)

Time: Estimated to be from the time of informed consent for approximately 2.5 years

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Description: The DCR will be estimated by the proportion of disease control. Disease control is defined as CR, PR or stable disease.

Measure: Disease Control Rate (DCR)

Time: Estimated to be from the time of informed consent for approximately 2.5 years

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Description: The DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.

Measure: Duration of Response (DoR)

Time: Estimated to be from the time of informed consent for approximately 2.5 years

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Description: The TTR is defined as the time from the start of treatment with any investigational product until the first documentation of a subsequently confirmed objective response.

Measure: Time To Response (TTR)

Time: Estimated to be from the time of informed consent for approximately 2.5 years

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Description: PFS will be measured from the start of treatment with any investigational product until the first documentation of disease progression or death due to any cause, whichever occurs first.

Measure: Progression Free Survival (PFS)

Time: Estimated to be from the time of informed consent for approximately 2.5 years

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Description: OS will be measured from the start of treatment with investigational product until death due to any cause.

Measure: Overall Survival (OS)

Time: Estimated to be from the time of informed consent for approximately 2.5 years

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Description: MEDI5395 concentrations in blood will be tabulated by dose cohort along with descriptive statistics.

Measure: MEDI5395 viral genome copies in blood collected over time

Time: Estimated to be from the time of informed consent for approximately 6 months

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Description: GM-CSF protein concentrations in blood will be tabulated by dose cohort along with descriptive statistics.

Measure: Granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations in blood collected over time

Time: Estimated to be from the time of informed consent for approximately 6 months

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Description: Immunogenic response to MEDI5395 will be assessed by summarizing the number of subjects who develop detectable anti-MEDI5395 neutralizing antibodies

Measure: Number of subjects who develop detectable anti-MEDI5395 neutralizing antibodies

Time: Estimated to be from the time of informed consent until approximately 90 days after the last dose of last investigational product

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Description: Immunogenic response to MEDI5395 will be assessed by summarizing the percentage of subjects who develop detectable anti-MEDI5395 neutralizing antibodies

Measure: Percentage of subjects who develop detectable anti-MEDI5395 neutralizing antibodies

Time: Estimated to be from the time of informed consent until approximately 90 days after the last dose of last investigational product

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Description: CD8 T cell infiltration and PD-L1 expression in tumors pre and post dosing will be assessed using validated IHC assays.

Measure: The number of cluster of differentiation 8 (CD8) positive cells and programmed death-ligand 1(PD-L1) expressing cells within biopsies will be assessed.

Time: Estimated to be from the time of informed consent until 4 weeks after the first dose of MEDI5395

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Primary Outcomes

Description: Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.

Measure: Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with pancreatic cancer.

Time: Within 6 months of treatment onset

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Description: Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.

Measure: Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with virus associated tumors.

Time: Within 6 months of treatment onset

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Description: Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.

Measure: Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with non-small cell lung cancer.

Time: Within 6 months of treatment onset

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Description: Antitumor activity will be assessed in terms of 6-month progression-free rat (PFR) and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed at 6 months following treatment onset and more than 24 weeks, based on RECIST 1.1 criteria.

Measure: Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with soft-tissue sarcoma.

Time: 6 months of treatment onset

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Description: Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.

Measure: Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with bladder cancer.

Time: Within 6 months of treatment onset

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Description: Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.

Measure: Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with triple negative breast cancer.

Time: Within 6 months of treatment onset

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Secondary Outcomes

Description: Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.

Measure: 6-month Progression-free rate (PFR) in patients with pancreatic cancer.

Time: 6 months

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Description: Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.

Measure: 6-month Progression-free rate (PFR) in patients with virus-associated tumor.

Time: 6 months

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Description: Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.

Measure: 6-month Progression-free rate (PFR) in patients with non-small cell lung cancer.

Time: 6 months

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Description: Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.

Measure: 6-month Progression-free rate (PFR) in patients with bladder cancer.

Time: 6 months

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Description: Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.

Measure: 6-month Progression-free rate (PFR) in patients with triple negative breast cancer.

Time: 6 months

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Description: Objective response is defined as the proportion of patients with complete response (CR) or partial response (PR) observed at 6 months, based on RECIST 1.1 criteria.

Measure: 6-month objective response rate (ORR) independently for each population.

Time: 6 months

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Description: Objective response is defined as the proportion of patients with complete response (CR) or partial response (PR) observed within 24 wekks after treatment onset, based on RECIST 1.1 criteria.

Measure: Objective response rate (ORR) within 24 weeks of treatment onset, independently for each population.

Time: Within 6 months

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Description: Best overall response is defined as the best response across all time points (RECIST 1.1). The best overall response is determined once all the data for the patient is known (RECIST 1.1).

Measure: Best overall response, independently for each population.

Time: Throughout the treatment period, an expected average of 6 months

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Description: Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST 1.1) or death (from any cause), whichever occurs first.

Measure: 1-year progression-free survival, independently for each population.

Time: 1 year

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Description: Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST 1.1) or death (from any cause), whichever occurs first.

Measure: 2-year progression-free survival, independently for each population.

Time: 2 years

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Description: Overall survival is defined as the delay between the start date of treatment and the date of death (of any cause).

Measure: 1-year overall survival, independently for each population.

Time: 1 year

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Description: Overall survival is defined as the delay between the start date of treatment and the date of death (of any cause).

Measure: 2-year overall survival, independently for each population.

Time: 2 years

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Description: Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.

Measure: Safety profile, independently for each population: Common Terminology Criteria for Adverse Events version 5

Time: Throughout the treatment period, an expected average of 6 months

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Description: Levels of immune cells in tumor will be measured by immunohistochemistry.

Measure: Tumor immune cells levels

Time: before treatment onset and cycle 3 day 1 (each cycle is 21 days)

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Description: Levels of cytokines in blood will be measured by ELISA.

Measure: Blood cytokines levels

Time: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days)

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Description: Levels of lymphocytes in blood will be measured by flow cytometry.

Measure: Blood lymphocytes levels

Time: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days)

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Description: Levels of kynurenine in blood will be measured by ELISA.

Measure: Blood kynurenine levels

Time: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days)

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Primary Outcomes

Description: FACIT Spiritual Well-Being Scale is a brief self-report measure designed to assess the nature and extent of individual spiritual well-being. This measure, which generates two sub-scales, one corresponding to Faith (the importance of faith and spirituality) and a second assessing Meaning-Peace (one sense of meaning and purpose in life), has been demonstrated to have strong internal reliability for both the total score as well as each subscale (coefficient alpha equals .87 for the total scale, .88 for the faith factor and .81 for the meaning factor). In additional, strong support for the external validity of this measure has been demonstrated in a several large samples of cancer and AIDS patients and with Spanish speaking populations.

Measure: Spiritual Well-Being measured with the FACIT Spiritual Well-Being Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Secondary Outcomes

Description: The Hospital Anxiety and Depression Scale (HADS) is a validated scale used to measure anxiety and depression. This scale has been validated against structured or semi-structured clinical interviews, the gold standard for the assessment of mental disorders, in a significant number of studies. Further strengths of this scale for the assessment of emotional distress in cancer patients stem from the joint assessment of anxiety and depressive symptoms without referring to physical symptoms of anxiety or depression. Given the high comorbidity of anxiety of cancer as well as the systematic exclusion of confounding physical symptoms, the scale seems especially appropriate for use in this patient group. The HADS consists of 14 items which reflect a 7-item anxiety and a 7-item depression subscale. This scale has sound psychometric properties in Spanish.

Measure: Depression and Anxiety measured with the Hospital Anxiety and Depression Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Description: The Beck Hopelessness Scale (BHS) comprises 20 true/false questions that assess degree of pessimism and hopelessness. Several studies have demonstrated a high degree of internal consistency and construct validity. Scores ranging from 4 to 8 typically indicate a "mild" degree of hopelessness, 9 to 12 correspond to "moderate" hopelessness, and scores about 12 reflect "severe" levels of hopelessness.

Measure: Hopelessness measured with the Beck Hopelessness Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Description: The FACIT Spiritual Well-Being Scale (FACIT-Sp-12) is a brief self-report measure designed to assess the nature and extent of individual's spiritual well-being. This measure (range 0-48), which generates two sub-scales, Faith (the importance of faith/spirituality, range 0-16) and Meaning /Peace (one's sense of meaning and purpose in life, range 0-32). The total score for the FACIT-Sp scale is the sum of the two subscales Faith and Meaning /Peace. It has been demonstrated to have strong internal reliability for both the total score as well as each subscale (coefficient alpha = .87 for the total scale, .88 for the faith factor and .81 for the meaning factor). Higher scores represent a higher level of spiritual well-being, faith or meaning-peace. In addition, strong support for the external validity of this measure has been demonstrated in a several large samples of cancer and AIDS patients and with Spanish speaking populations. Administration time takes approximately 4 minutes.

Measure: Quality of life measured with the FACIT Spiritual Well-Being Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Primary Outcomes

Description: The primary outcome is the proportion of patients who have a goals-of-care (GOC) discussion that has been documented in the EHR in the period between randomization and 30 days following randomization The proportion is the number of patients with GOC documentation over the number of patients in each study arm. Documentation of goals-of-care discussions will be evaluated using our NLP/ML methods. Study staff will manually review and compare findings using a randomly-selected sample of charts using our standard EHR abstraction methods; manual chart abstraction will be the gold standard.

Measure: EHR documentation of Goals of Care discussions

Time: Assessed for the period between randomization and 30 days following randomization

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Secondary Outcomes

Description: Secondary outcomes include measures of intensity of care, including utilization metrics: Number of ICU admissions during the patient's (index) hospital stay will be collected from the EHR using our automated and validated methods.

Measure: Intensity of care/ICU use: ICU admissions

Time: Assessed for the period between randomization and 30 days following randomization

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Description: Secondary outcomes include measures of intensity of care, including utilization metrics: Number of days the patient spent in the ICU during their (index) hospital stay will be collected from the EHR using our automated and validated methods.

Measure: Intensity of care/ICU use: ICU length of stay

Time: Assessed for the period between randomization and 30 days following randomization

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Description: Secondary outcomes include measures of intensity of care, including utilization metrics: Number of days the patient spent in the hospital during that (index) hospital stay will be collected from the EHR using our automated and validated methods.

Measure: Intensity of care/Hospital use: Hospital length of stay

Time: Assessed for the period between randomization and 30 days following randomization

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Description: Secondary outcomes include measures of intensity of care, including utilization metrics: Number of hospital readmissions between randomization and 30 days following randomization will be collected from the EHR using our automated and validated methods.

Measure: Intensity of care: Hospital Readmissions 30 days

Time: Assessed for the period between randomization and 30 days following randomization

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Description: Secondary outcomes include measures of intensity of care, including utilization metrics: Number of ICU readmissions between randomization and 30 days following randomization will be collected from the EHR using our automated and validated methods.

Measure: Intensity of care: ICU Readmissions 30 days

Time: Assessed for the period between randomization and 30 days following randomization

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Description: Costs for intervention vs. control will be reported in US dollars and identified from UW Medicine administrative financial databases. Costs will be reported for total hospital costs and disaggregated costs (direct-variable, direct fixed, indirect costs). Direct-variable costs will include supply and drug costs. Direct-fixed costs will include labor, clinical department administration, and overhead fees. Indirect costs represent services provided by cost centers not directly linked to patient care such as information technology and environmental services. Costs for ED (emergency department) days and ICU days will be similarly assessed.

Measure: Intensity of care: Healthcare costs

Time: 1 and 3 months after randomization

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Description: From Washington State death certificates.

Measure: All-cause mortality at 1 year (safety outcome)

Time: 1 year after randomization

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Other Outcomes

Description: Qualitative interviews after individual participation. Interviews will be guided by the RE-AIM and Consolidated Framework for Implementation Research (CFIR) to explore the factors associated with implementation (e.g., reach, maintenance, feasibility, inner and outer settings, individuals, and processes of care.) Individual constructs within these domains were chosen to fit this specific intervention and context.

Measure: Key Implementation Factors

Time: 3 months after randomization

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Primary Outcomes

Description: Incidence rate of SARS-CoV-2 infection within the whole period of the study.

Measure: SARS-CoV-2 infection

Time: through study completion, an average of 3 months.

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Secondary Outcomes

Description: Tumor response by determining changes (PD, SD, PR, CR) according to Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1

Measure: Tumor response

Time: 6 weeks after enrollment.

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Description: Safety and tolerability of chemotherapy as measured by the Common Terminology Criteria for Adverse Events (version 4.0)

Measure: Safety and tolerability of chemotherapy as measured by the Common Terminology

Time: through study completion, an average of 3 months.

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Description: To evaluate quality of life (QOL) for the subjects undergoing this treatment, using validated tools. QOL will be assessed every 3 months during treatment course. [Functional Assessment of Cancer Therapy - Ovarian Cancer questionnaire (score range from 0 to 160. Higher scores represent better quality of life. questionnaire core-30 (QLQ-C30).

Measure: Quality of Life (QOL) measures using Functional Assessment of Cancer Therapy (FACT- ovarian cancer)

Time: through study completion, an average of 3 months.

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Primary Outcomes

Description: modification of the planned therapeutic management

Measure: percentage of patients with a change in the planned therapeutic management (surgery, chemotherapy, radiotherapy, hormone therapy)

Time: Day O

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Primary Outcomes

Description: The percentage of HM patients with COVID-19 who died.

Measure: To evaluate mortality.

Time: At 2 months from study initiation

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Description: We will assess the correlation between some biochemical parameters at diagnosis of COVID (i.e. hemoglobin, platelets, lymphocytes, clotting tests, CRP), each on the basis of its specific unit of measure, and mortality.

Measure: To evaluate potential predictive biochemical parameters of mortality.

Time: At 2 months from study initiation

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Description: We will assess the correlation between HM-related parameters at diagnosis of COVID [i.e. disease type (leukemia, lymphomas, myeloma), disease status (remission / stable / progression), therapy status (on / off therapy)] and mortality.

Measure: To evaluate potential predictive HM-related parameters of mortality.

Time: At 2 months from study initiation

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Description: We will assess the correlation between COVID severity [mild (non-pneumonia and mild pneumonia), severe (dyspnea, respiratory frequency ≥ 30/min, SpO2 ≤ 93%, PaO2/FiO2 < 300 and/or lung infiltrates > 50%) and critical (respiratory failure, septic shock, and/or multiple organ disfunction or failure)] and mortality

Measure: To evaluate COVID severity as predictive parameter of mortality.

Time: At 2 months from study initiation

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Secondary Outcomes

Description: Description of the different types of hematological malignancies (WHO criteria) in patients with SARS-CoV-2 infection. All aggregated data will be stratified on the basis of COVID severity: mild (non-pneumonia and mild pneumonia), severe (dyspnea, respiratory frequency ≥ 30/min, SpO2 ≤ 93%, PaO2/FiO2 < 300 and/or lung infiltrates > 50%) and critical disease (respiratory failure, septic shock, and/or multiple organ disfunction or failure)

Measure: Epidemiology of patients with HM infected by SARS-CoV-2with any spectrum of illness severity

Time: At 6 months from study initiation

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Description: Characterization of clinical and biochemical profile of patients with SARS-CoV-2 positivity.

Measure: Definition of complete clinical picture of COVID-19 in HM

Time: At 2 months from study initiation

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Description: Assessment of HM status post SARS-CoV-2 infection stratified as no implication, loss of response, progression of the hematological disease.

Measure: Evolution of HM

Time: At 2 months from study initiation

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Description: Percentage of HM patients being admitted to ICU requiring mechanical ventilation, or death stratified per disease type, status, per off-therapy/on-therapy, per type of therapy (chemo, immunotherapy, cell therapy, stem cell transplant).

Measure: To evaluate admission to ICU requiring mechanical ventilation or death per characteristics

Time: At 2 months from study initiation

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Measure: Viral dynamics in infected HM patients

Time: At 12 months from study initiation

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Primary Outcomes

Description: The survey includes five parts: 1) basic demographics about the patient, including performance status and comorbidities; 2) initial COVID-19 diagnosis and clinical course; 3) cancer and cancer treatment details; 4) respondent details; 5) long-term COVID-19 outcomes.

Measure: Web-based REDCap survey

Time: Approximately 18 months

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Primary Outcomes

Description: The 7-day length of invasive MV for each arm will be estimated with 95% confidence intervals (CIs) using the exact binomial distribution. Their difference by the arms will be tested by Cochran-Mantel-Haenszel (CMH) test stratified by the age group and Sequential Organ Failure Assessment (SOFA) score at significance level of 0.05.

Measure: 7-day length of invasive mechanical ventilation (MV)

Time: Up to 7 days

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Description: Defined as death within 30-day after randomization. The 30-day mortality rate for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.

Measure: 30-day mortality rate

Time: Up to 30-day after randomization

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Secondary Outcomes

Description: The rate of ICU transfer for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.

Measure: Rate of intensive care (ICU) transfer

Time: Up to 2 years

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Description: The rate of invasive mechanical ventilation for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.

Measure: Rate of invasive mechanical ventilation

Time: Up to 2 years

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Description: The rate of tracheostomy for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.

Measure: Rate of tracheostomy

Time: Up to 2 years

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Description: Will first be described by median and inter-quartile, and then compared between two arms by Wilcoxon Sum-Rank test

Measure: Length of ICU stay

Time: Up to 2 years

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Measure: Length of hospital stay

Time: Up 2 years

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Primary Outcomes

Description: The primary endpoint of this study is the recurrence of COVID-19 within 3 months following the immunoassay-positive result obtained before the inclusion in the study. The recurrence is defined by the presence of symptoms confirmed either by a positive reverse transcription-polymerase chain reaction (RT-PCR) result for SARS-CoV-2 or by the adjudication committee. Immunoassay will be said positive as per the predefined reference corresponding to the immunoassay.

Measure: To evaluate the ability of SARS-CoV-2 immunoassays, following a positive result, to identify patients with very low risk of recurrence of COVID-19 within 3 months.

Time: 3 months

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Secondary Outcomes

Description: The prevalence is the ratio between the number of immunoassay-positive patients and the number of patients tested over a predefined period, i.e the whole duration of the study and by 1-month intervals.

Measure: To estimate the prevalence of patients immunized to the SARS-CoV-2 virus in an oncology population over the whole study duration and within one-month periods.

Time: 6 months

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Description: Agreement between the different immunoassays and the centralized ELISA, using the centralized ELISA as benchmark.

Measure: To estimate the discordance rate between local immunoassay and a centralized ELISA in patients with a positive immunoassay, whatever the immunoassay.

Time: 6 months

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Description: COVID-19 recurrence within 6 months following an immunoassay-positive result.

Measure: To identify patients with very low risk of recurrence of COVID-19 within 6 months following a positive immunoassay result.

Time: 6 months

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Description: Quantitative and qualitative detection of SARS-CoV-2-related antibodies and immune serum markers at baseline, 2-3 months and 4-6 months post-inclusion, in a subgroup of 200 patients.

Measure: To characterize the evolution over time of the serologic response against SARS-CoV-2 (in a subgroup of patients).

Time: 6 months

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Primary Outcomes

Description: Number of participants in dose escalating arm with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

Measure: Safety and tolerability of T3011 in dose escalating administration in patients with advanced cutaneous or subcutaneous malignancies

Time: From first dose of T3011 (Week 1 Day 1) until 60 days after the last T3011 injection (up to 2 years)

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Description: Number of participants in dose expansion arm with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

Measure: Safety and tolerability of T3011 in dose expansion administration in patients with advanced cutaneous or subcutaneous malignancies

Time: From first dose of T3011 (Week 1 Day 1) until 60 days after the last T3011 injection (up to 2 years)

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Secondary Outcomes

Description: To evaluate the virus shedding following intratumoral injection

Measure: Presence and frequency of T3011 in serum, saliva, urine, and injection site/dressing

Time: Up to 24 months

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Description: To evaluate IL-12 and anti-PD-1 antibody expression of T3011 post intervention.

Measure: Quantitative measurements of serum IL-12 and anti-PD-1 antibody concentration.

Time: Up to 24 months

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Description: To evaluate the immunogenicity of anti-PD-1 antibody expressed by T3011 post intervention.

Measure: Presence of neutralizing antibodies of anti-PD-1 antibody for antidrug antibodies (ADAs) development

Time: Up to 24 months

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Description: To evaluate the immunogenicity of T3011 viral vector post intervention.

Measure: Presence of anti-herpes simplex virus type 1 (HSV-1) antibody compared to baseline

Time: Up to 24 months

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Description: ORR is defined as the proportion of participants who have a partial response (PR) or complete response (CR) to intervention, based on assessments per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Measure: Overall response rate (ORR)

Time: Up to 24 months

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Description: DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments per RECIST 1.1.

Measure: Disease control rate (DCR)

Time: Up to 24 months

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Description: DOR is defined as the time from the first met CR or PR until disease progression or death due to any cause, whichever occurs first.

Measure: Duration of response (DOR).

Time: Up to 24 months

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Description: DR is defined as objective response (CR or PR) according to RECIST 1.1, with a duration of at least 6 months.

Measure: Durable response (DR)

Time: Up to 24 months

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Description: To evaluate the progression free survival (PFS) and overall survival (OS) of participants.

Measure: Survival (assessment per RECIST 1.1 and immune-modified RECIST (imRECIST)).

Time: Up to 24 months

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Primary Outcomes

Measure: Clinical outcome as evaluated by the 7-category Clinical Status Ordinal Scale

Time: At least 60 days, up to 1 year

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Primary Outcomes

Description: This refers to the frequency of grade 3 or 4 AEs considered to be possibly, probably or definitely related to the treatment regimen. Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE version [v] 5.0).

Measure: Incidence of adverse events (AEs)

Time: Up to 30 days post treatment intiation

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Description: will be evaluated based on quantitative polymerase chain reaction PCR

Measure: Kinetics of viral load in nasopharyngeal swabs

Time: Up to 30 days post treatment initiation

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Secondary Outcomes

Description: Will be analyzed using quantitative polymerase chain reaction (PCR).

Measure: Kinetics of viral load in the peripheral blood and nasopharyngeal swabs

Time: During the course of treatment up to day 30

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Description: The circulatory inflammatory mediators include C-reactive protein (CRP), cytokines, chemokines, interferons.

Measure: Kinetics of changes of the immune subsets and circulating inflammatory mediators in peripheral blood

Time: During the course of treatment up to day 30

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Description: The binary endpoint of 30-day mortality will be analyzed using a logistic regression model.

Measure: 30-day mortality

Time: At 30 days post treatment initiation

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Description: Rate of hospitalization due to infection

Measure: Hospitalization due to infection

Time: Up to 30 days post treatment initiation

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Description: Will be tested in nasopharyngeal swabs and blood cells of patients

Measure: Determine known mediators of antiviral immunity

Time: UP to 30 days post treatment initiation

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Other Outcomes

Description: ARDS will be defined by Berlin criteria

Measure: acute respiratory distress syndrome (ARDS)

Time: Up to 30 days post treatment initiation

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Description: Need for mechanical ventilation

Measure: respiratory failure requiring mechanical ventilation

Time: up to 30 days post treatment initiation

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Primary Outcomes

Description: Incidence of cases of MPN patients with COVID-19 experiencing pulmonary embolism

Measure: pulmonary embolism (PE)

Time: 2 and a half months

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Secondary Outcomes

Description: Incidence of cases reporting at least one fatal or non fatal thrombotic event reported in therapy of MPN

Measure: fatal or non fatal thrombotic event

Time: 2 and a half months

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Description: Incidence of cases reporting at least one COVID-19 worsening outcome as Continuous Positive Airway Pressure (CPAP)

Measure: Continuous Positive Airway Pressure (CPAP)

Time: 2 and a half months

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Description: Incidence of cases reporting at least one COVID-19 worsening outcome as invasive ventilation

Measure: invasive ventilation

Time: 2 and a half months

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Description: Incidence of cases reporting at least one COVID-19 worsening outcome as Intensive Care Unit (ICU)

Measure: admission in Intensive Care Unit (ICU)

Time: 2 and a half months

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Description: incidence of death

Measure: death

Time: 2 and a half months

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Description: Type of treatments and interventions applied for MPN during COVID-19 and any change reported in therapy of MPN

Measure: treatments and interventions applied for MPN

Time: 2 and a half months

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Description: Type of treatments and interventions applied for COVID-19

Measure: treatments and interventions applied for COVID-19

Time: 2 and a half months

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Description: Odds Ratios (ORs) of the outcome and 95% Confidence Intervals (CIs) associated with patients' characteristics and treatments

Measure: thrombotic events association to patients characteristic and treatments

Time: 2 and a half months

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Primary Outcomes

Description: Distinguish the likelihood of severe COVID19 (for example, requiring hospitalization, requiring intensive care unit [ICU] treatment or requiring a ventilator) and death due to COVID-19 for patients with versus without the factor. Among subgroups of at least 50 patients, evaluate using chi-square tests as well as death and hospitalization rates.

Measure: Patient variables (factors) associated with severe acute respiratory syndrome (SARS) coronavirus 2 (COVID-19) severity

Time: Up to 2 years

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Description: Describe the degree to which COVID-19 interrupts, delays, or otherwise alters cancer treatment for pediatric patients and subgroups of adult patients defined by cancer type and/or treatment modality. Describe the association between changes in cancer therapy and clinical outcomes. Evaluate association of COVID-19 with outcome by comparison to historical controls in subgroups of at least 50 patients using log rank tests to assess time to survival event.

Measure: Effects of COVID-19 on cancer therapy and association with clinical outcomes

Time: Up to 2 years

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Description: Will be measured using items from the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 Profile.

Measure: Physical health (patient-reported health-related quality of life)

Time: Up to 2 years

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Other Outcomes

Description: Analysis will include time to development of antibodies, prevalence of cytokine abnormalities, and genome-wide association study (GWAS) to define genetic polymorphisms associated with severe COVID-19 disease/mortality.

Measure: Collection of blood specimens for future biomarker studies

Time: Up to 2 years

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Primary Outcomes

Description: Locally evaluated rate of viral response. Favorable response is defined as (1) complete response : negative PCR (absence of detectable signal with a minimum of 40 cycles) or (2) major response : detectable signal but with an increased number of cycles > or egal to 10 compared to initial PCR. Response failure is defined as (1) minor response : detectable signal but with an increased number of cycles < 10 compared to initial PCR or (2) stabilisation or worsening of the viral load.

Measure: Evaluation of the efficacy of hydroxychloroquine and azithromyncine on the viral load drop at day 5.

Time: 5 days of treatment

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Secondary Outcomes

Description: Duration of fever - duration of respiratory symptoms (cough, dyspnea) - duration of other COVID-19 related symptoms (digestive symptoms, ageusia, anosmia)

Measure: Clinical evolution

Time: up to 3 months

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Description: Less or equal to 94% oxygen saturation - need to initiate oxygenotherapy - occurrence of respiratory distress - patient transfer in intensive care unit - need of mechanical ventilation - occurrence of non-respiratory organ failure - occurrence of septic shock

Measure: Proportion of patients progressing to a severe form

Time: up to 3 months

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Description: Date and cause of death

Measure: Mortality

Time: up to 1 and 3 months

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Description: SARS-CoV-2 viral load by PCR on nasopharyngeal swab at day 10 (if positive at day 5) : rate of negativation and comparison of number of cycles with previous samples

Measure: Evaluation of viral load drop

Time: at day 10

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Description: Frequence and causality of all-grade cardiac adverse events - frequence and causality of grade > 1 adverse events for other adverse events - frequence and causality of serious adverse events (CTCAE v5)

Measure: Tolerance of study treatment

Time: up to 3 months

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Description: Collection of serum to realize serological tests

Measure: Evaluation of the seroconversion

Time: at inclusion, day 10, day 30 and day 90 after treatment

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Description: Phenotypic and functional study of NK lymphocytes at inclusion, Retrospective analysis on frozen cells.

Measure: NK immunological study

Time: at day 10 and day 30 after treatment

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Description: Duration of hospitalisation (conventional, intensive care, reanimation)

Measure: Hospitalisation duration

Time: up to 3 months

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Description: Patient follow-up during 3 months : hematological status and associated therapy

Measure: Impact of the study treatment on the treatment of the hematological disease

Time: up to 3 months

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Description: ECG (using connected machine to allow monitoring at home)

Measure: Monitoring of the QT space

Time: at inclusion, day 2, day 5, day 10

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Description: Dosage of residual concentration of azithromycine and hydroxychloroquine.

Measure: Dosage of residual concentration of azithromycine and hydroxychloroquine.

Time: at day 5 and day 10

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Description: Phenotypic and functional study of T lymphocytes at inclusion, Retrospective analysis on frozen cells.

Measure: T immunological study

Time: at day 10 and day 30 after treatment

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Primary Outcomes

Description: To focus on basic issues encountered by oncology patients such as transportation, medical facility, healthcare support, disease apprehension etc

Measure: Oncology patients

Time: 4-8 weeks

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Primary Outcomes

Description: Describe the incidence of patients with a positive test for SARS-CoV-2, detected in the preoperative screening program in our center

Measure: Incidence of patients with a positive test for SARS-CoV-2, detected in the preoperative screening program

Time: May- December 2020

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Secondary Outcomes

Description: Describe the incidence of SARS-CoV-2 infection in the postoperative period in patients with negative screening test.

Measure: Incidence of SARS-CoV-2 infection in the postoperative period in patients with negative screening test;

Time: Up to 30 days

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Description: Postoperative complications will be recorded, according to the Clavien-Dindo classification.

Measure: Postoperative complications

Time: Up to 30 days

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Description: To evaluate the risk of all-cause mortality

Measure: Mortality

Time: 30 days

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Description: Assess the impact of delayed cancer treatment

Measure: Delay in the cancer treatment

Time: May 2020- March 2021

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Primary Outcomes

Description: Evaluation of the proportion of patients with COVID-19 infection's symptoms known to be associated with COVID-19 diagnosis (fever, cough, loss of taste and smell, sore throat, muscle pain, diarrhea, fatigue, difficulty eating and drinking and shortness of breath) followed during a period of 6 months.

Measure: COVID-19 infection's symptoms

Time: Observational period of 6 months

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Secondary Outcomes

Description: To assess the prevalence and course of symptoms of COVID-19 infection of patients followed during a period of 6 months.

Measure: Incidence and course of symptoms of COVID-19 infection

Time: During a period of 6 months

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Description: To establish the correlation of the COVID-19 infection with the biological and clinical data of patients from the Oncology cohort of the Groupe hospitalier Paris Saint-Joseph in Paris followed during a period of 6 months.

Measure: Correlation of the COVID-19 infection with the biological and clinical data of patients

Time: After a period of 6 months

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Primary Outcomes

Description: Associations between baseline characteristics and the primary endpoint will be evaluated with logistic regression, adjusting for arm. These analyses will be largely descriptive, as a result of a limited sample size.

Measure: Proportion of patients with diminished respiratory failure and death

Time: During hospitalization for COVID-19 infection or within 30 days of registration

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Measure: Death

Time: During hospitalization for COVID-19 infection or within 30 days of registration

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Secondary Outcomes

Description: Fever-free will be assessed by a temperature of < 100.5 degrees Fahrenheit orally. Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.

Measure: Time from study initiation to 48 hours fever-free

Time: Up to 14 days

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Description: Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.

Measure: Duration of hospitalization

Time: Up to 14 days

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Measure: Time in intensive care unit (ICU)

Time: Up to 14 days

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Measure: Time to ICU admission

Time: Up to 14 days

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Measure: Number of days requiring supplemental oxygen

Time: Up to 14 days

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Measure: Total days of mechanical ventilation

Time: Up to 14 days

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Measure: Time to mechanical ventilation

Time: Up to 14 days

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Measure: Shock and need for pressure support

Time: Up to 14 days

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Measure: Incidence of any infection (viral, fungal, bacterial)

Time: Up to 14 days

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Measure: Time to clinical resolution

Time: Up to 14 days

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Description: Adverse events will be summarized by grade, type, and attribution (regardless of attribution and treatment-related) for each arm.

Measure: Incidence of grade 3 or higher adverse events

Time: Up to 12 months

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Description: The proportion of patients with viral clearance at the time of hospital discharge will be estimated with 95% confidence intervals for each arm.

Measure: At the end of therapy (day 14)

Time: Up to 14 days

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Description: Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.

Measure: Time to viral clearance

Time: Up to 12 months

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Description: Patients will be followed for up to 12 months or until death or withdrawal of study consent for further follow-up. Following hospitalization, study visits will be telephone or video encounters.

Measure: Survival

Time: Up to12 months

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Primary Outcomes

Description: Will be compared to the time of randomization. The severity of symptoms will be categorized as mild, moderate, severe, or critical according to the grading of symptoms. The proportion of participants with progression to more severe symptoms between treatments groups will be compared using a Fisher's Exact test at a 0.05 significance level.

Measure: Severity of symptoms

Time: 3 months

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Secondary Outcomes

Description: Will be defined as improvement on symptoms: yes or no. Will be compared between treatment groups using log-rank test. A 95% confidence interval of treatment rate difference in symptom progression will be calculated by the Wald method.

Measure: Clinical benefit rate of lopinavir/ritonavir

Time: 3 months

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Description: Will be compared between treatment groups using log-rank test.

Measure: Time to symptom progression

Time: From randomization to the first documented symptoms progression, assessed up to 3 months

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Description: Will be compared between treatment groups using log-rank test.

Measure: Time to improvement of participants

Time: From randomization to first documented complete resolution of symptoms, assessed up to 3 months

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Description: Will be compared between treatment groups using log-rank test.

Measure: Time to hospital admission for those who develop severe of critical symptoms

Time: From time of randomization to the time of hospital admission, assessed up to 3 months

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Description: Will be compared using Fisher's exact test, and point and interval estimates will be provided.

Measure: Intensive care unit (ICU) admission: yes or no

Time: 3 months

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Description: Will be compared using Fisher's exact test, and point and interval estimates will be provided.

Measure: Receiving ventilator support: yes or no

Time: 3 months

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Description: Will be compared using Fisher's exact test, and point and interval estimates will be provided.

Measure: Overall survival

Time: From randomization to death due to any cause, assessed up to 3 months

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Other Outcomes

Description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.

Measure: Potassium level

Time: 3 months

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Description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.

Measure: Blood oxygen level

Time: 3 months

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Description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.

Measure: Creatinine level

Time: 3 months

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Description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.

Measure: Blood pressure

Time: 3 months

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Description: Will evaluate on a subjective basis the ability to remotely consent, monitor and treat patients in the context of a pandemic of a contagious disease. The proportion of participants able to be remotely consented, monitored, and treated in the context of a pandemic of a contagious disease will be tabulated and compared using the chi-square test.

Measure: Ability to remotely consent, monitor, and treat patients in the context of a pandemic of a contagious disease

Time: 3 months

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Primary Outcomes

Description: Retrospective chart review of health care utilization of both groups

Measure: Health Care Utilization Comparison

Time: 5 months

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Secondary Outcomes

Description: Patient Reported Outcomes Measurement Information System- Short Form v2.0 Social Isolation- 6a. The PROMIS Social Isolation item bank assesses perceptions of being avoided, excluded, detached, disconnected from, or unknown by, others. The item bank does not use a time frame (e.g. over the past seven days) when assessing social isolation. A higher PROMIS T-score represents more of the concept being measured. For negatively-worded concepts like Social Isolation, a T-score of 60 is one SD worse than average. By comparison, a Social Isolation Tscore of 40 is one SD better than average.

Measure: Patient Social Isolation

Time: Monthly for 5 months

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Description: Patient reported outcomes collected in automated SCH system daily of COVID-19 symptoms, social distancing and hygiene practices, and COVID-19 related cancer treatment impacts and daily living impacts on cancer patients receiving the SCH -COVID intervention. The investigators will describe patterns of cancer patients and their adherence to social distancing and hygiene practices over time.

Measure: COVID-19 Symptoms, Social distancing and Hygiene Practices

Time: Daily for 5 months

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Description: Patient Reported Outcomes Measurement Information System Scale v1.2- Global Health Survey Short Form 10. High scores reflect better functioning. To find the total raw score for these scales with all questions answered, sum the values of the response to each question for a given respondent.

Measure: Patient Global Health

Time: Monthly 5 months

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Description: Hospital Anxiety and Depression Scale (HADS) measurement of psychological distress in non-psychiatric patients.

Measure: Patient Anxiety/Depression

Time: Monthly 5 months

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Description: COVID-19: Impact of the Pandemic and Health Related Quality Of Life (HRQOL) in Cancer Patients and Survivors

Measure: Impact of Pandemic and Health Related Quality of Life

Time: Baseline then 3 months and 5 months from baseline

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Description: Patient reported outcomes collected in automated SCH system daily of cancer symptom severity on a scale of 0-10 with 0 being no pain and 10 being worst pain imaginable. Description of symptom severity over time will be reported

Measure: Cancer symptom severity

Time: Daily for 5 months.

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Primary Outcomes

Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: Experiences during the coronavirus disease 2019 (COVID-19) pandemic

Time: 2 months

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Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: COVID-19-specific psychological distress

Time: Up to 2 months

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Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: COVID-19-specific health

Time: Up to 2 months

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Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: COVID-19-specific financial and social disruptions

Time: Up to 2 months

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Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: COVID-19-specific perceived benefits and social support

Time: Up to 2 months

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Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: COVID-19-specific health related quality of life (HRQoL)

Time: Up to 2 months

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Description: Will evaluate the extent to which resiliency factors such as social support and perceived benefits moderate the effects of COVID-19 experiences on COVID-19-specific psychological distress and HRQoL.

Measure: Effects of COVID-19 experiences on COVID-19-specific psychological distress and HRQoL

Time: Up to 2 months

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Primary Outcomes

Description: Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study of treatment and reversibility or outcome.

Measure: Incidence of toxicity, graded according to the NCI CTCAE version 5

Time: Up to 28 days after completion of study treatment

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Description: Will be based on the assessment of dose limiting toxicity (DLT).

Measure: Maximum tolerated dose (MTD) (Phase 1)

Time: During the 28-day treatment period

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Description: Defined as a >= 2-point change in clinical status from day 1 on a 7-point ordinal scale.

Measure: Clinical activity (Response)(Phase 2)

Time: At day 28

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Secondary Outcomes

Description: Defined as time from start of treatment to >= 2 point change in clinical status on a 7 point ordinal scale

Measure: Time to Clinical activity (Response)

Time: Up to 28 days

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Description: Defined as time from start of treatment to death from any cause

Measure: Overall Survival

Time: Up to 90 days

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Description: Time from start of treatment to peripheral capillary oxygen saturation (SpO2) > 93% on room air

Measure: Oxygen Saturation improvement

Time: Up to 90 days

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Description: Time from start of treatment to first negative severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) result assessed by polymerase chain reaction (PCR).

Measure: SARS-CoV-2 resolution

Time: Up to 90 days

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Description: Hospitalized within first 90 days following start of treatment assessed as yes/no

Measure: Hospitalization

Time: Up to 90 days

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Description: Indication as to whether or not the subject required mechanical ventilation at any time from start of treatment through 90 days post; assessed as yes/no

Measure: Mechanical Ventilation required

Time: Up to 90 days

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Description: If the subject required mechanical ventilation, indicate number of days for first occurrence; measured in days.

Measure: Mechanical Ventilation duration

Time: Up to 90 days

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Description: Vital status will be reported as yes/no

Measure: Vital status (alive/dead)

Time: Up to 90 days

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Description: If vital status is dead, cause of death will be documented.

Measure: Vital status (cause of death)

Time: Up to 90 days

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Other Outcomes

Description: Measured by PCR assay of viral ribonucleic acid (RNA) from nasopharyngeal swab.

Measure: Viral load

Time: from start of treatment to 90 days

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Primary Outcomes

Description: FACIT Spiritual Well-Being Scale is a brief self-report measure designed to assess the nature and extent of individual spiritual well-being. This measure, which generates two sub-scales, one corresponding to Faith (the importance of faith and spirituality) and a second assessing Meaning-Peace (one sense of meaning and purpose in life), has been demonstrated to have strong internal reliability for both the total score as well as each subscale (coefficient alpha equals .87 for the total scale, .88 for the faith factor and .81 for the meaning factor). In additional, strong support for the external validity of this measure has been demonstrated in a several large samples of cancer and AIDS patients and with Spanish speaking populations.

Measure: Spiritual Well-Being measured with the FACIT Spiritual Well-Being Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Secondary Outcomes

Description: The Hospital Anxiety and Depression Scale (HADS) is a validated scale used to measure anxiety and depression. This scale has been validated against structured or semi-structured clinical interviews, the gold standard for the assessment of mental disorders, in a significant number of studies. Further strengths of this scale for the assessment of emotional distress in cancer patients stem from the joint assessment of anxiety and depressive symptoms without referring to physical symptoms of anxiety or depression. Given the high comorbidity of anxiety of cancer as well as the systematic exclusion of confounding physical symptoms, the scale seems especially appropriate for use in this patient group. The HADS consists of 14 items which reflect a 7-item anxiety and a 7-item depression subscale. This scale has sound psychometric properties in Spanish.

Measure: Depression and Anxiety measured with the Hospital Anxiety and Depression Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Description: The Beck Hopelessness Scale (BHS) comprises 20 true/false questions that assess degree of pessimism and hopelessness. Several studies have demonstrated a high degree of internal consistency and construct validity. Scores ranging from 4 to 8 typically indicate a "mild" degree of hopelessness, 9 to 12 correspond to "moderate" hopelessness, and scores about 12 reflect "severe" levels of hopelessness.

Measure: Hopelessness measured with the Beck Hopelessness Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Description: The FACIT Spiritual Well-Being Scale (FACIT-Sp-12) is a brief self-report measure designed to assess the nature and extent of individual's spiritual well-being. This measure (range 0-48), which generates two sub-scales, Faith (the importance of faith/spirituality, range 0-16) and Meaning /Peace (one's sense of meaning and purpose in life, range 0-32). The total score for the FACIT-Sp scale is the sum of the two subscales Faith and Meaning /Peace. It has been demonstrated to have strong internal reliability for both the total score as well as each subscale (coefficient alpha = .87 for the total scale, .88 for the faith factor and .81 for the meaning factor). Higher scores represent a higher level of spiritual well-being, faith or meaning-peace. In addition, strong support for the external validity of this measure has been demonstrated in a several large samples of cancer and AIDS patients and with Spanish speaking populations. Administration time takes approximately 4 minutes.

Measure: Quality of life measured with the FACIT Spiritual Well-Being Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Primary Outcomes

Description: Patients are asked before each session to mark in a numerical scale how are they feeling that day to push themselves and get their session well done. From 0 (very well) to 10 (very badly). Higher scores mean a worse feeling.

Measure: Suitability of exercise intensity

Time: Through study completion, an average of 3 months

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Description: Patients are asked to score the feeling of perceived effort after the session with the Borg Perceived Exertion scale (6-20). Higher scores mean a worse perceived exertion.

Measure: Verification of exercise intensity

Time: Through study completion, an average of 3 months

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Description: Total of days of attendance

Measure: Total attendance

Time: After intervention, an average of 3 months

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Description: Reasons of absence, categorized as: personal matter, visit the oncology, medical appointment (no related to oncology treatment), health problem, connection problem or unknown.

Measure: Absence type

Time: Through study completion, an average of 3 months

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Description: Attendance type, categorized as: full attendance, partly attendance because of lack of time, partly attendance because of internet connection problem

Measure: Attendance type

Time: Through study completion, an average of 3 months

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Secondary Outcomes

Description: The Spanish version of the Piper Fatigue Scale-Revised (PFS-R) will be used. Its total score is the sum of all items (from 0 to 220), with higher values indicate a higher level of fatigue (worse outcome)

Measure: Change from Cancer-Related Fatigue (CRF)

Time: Prior and after intervention, an average of 3 months

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Description: It will be tested by 30-second Sit-To-Stand Test (30-STS), number of repetitions completed.

Measure: Change from Functional capacity

Time: prior and after intervention, an average of 3 months

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Description: the Spanish version of Upper Limb Functional Index (ULFI) questionnaire will be filled online

Measure: Change from Upper limb functionality (%)

Time: prior and after intervention, an average of 3 months

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Description: the Spanish version of Lower Limb Functional Index (LLFI) questionnaire will be filled online

Measure: Change from Lower limb functionality (%)

Time: prior and after intervention, an average of 3 months

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Description: It will be assessed by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) version 3.0. EORTC QLQ-C30 comprises 30 items and contains five functional scales, three symptom scales, a global health status/QoL scale, and six single items. Raw scores can be linearly converted to a 0-100 scale with higher scores reflecting higher levels of function (better outcome) and higher levels of symptom show bigger problems (worse outcome).

Measure: Change from Quality of life (self-reported questionnaire)

Time: prior and after intervention, an average of 3 months

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Description: It will be assessed by The European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life questionnaire (EORTC QLQ-BR23). This is a breast cancer module of EORTC QLQ-C30 which contains 23 items that assess disease symptom, side effects of treatment, body image, sexual functioning, and future perspective. All items are rated on a 4-point scale (from 1- not at all, to very much). Higher scores represent better functioning (better outcome), and higher scores of symptom show bigger issues (worse outcome)

Measure: Change from specific Breast Cancer Quality of life (self-reported questionnaire)

Time: prior and after intervention, an average of 3 months

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Primary Outcomes

Description: Assessed per responses to the 12 questions pertaining to COVID-19 specific psychological stress within the adolescent and young adults (AYA) Cancer Survivor COVID-19 Survey section titled, "COVID-19 Related Distress (Emotional and Physical Reactions) and Health Behaviors.'' This survey includes both a 5-level Likert scale for the respondent's current level of concern (Not at all, A little, Neutral, A lot, Very Much), plus an ordinal 3-level scale for the respondent to rate the perceived level of change compared to before COVID-19 (Less, Same, More). Responses to individual questions will be summarized at each time point as means (for the Likert scale) and percentages (for discrete levels of change), together with 95% confidence intervals. For each question, will also summarize the percentages of patients in each group checking one of the 3 levels (Less, Same, More) indicating whether they perceived a change in that question since before COVID-19.

Measure: Coronavirus disease 2019 (COVID-19) specific psychological stress

Time: At baseline, 6 months, and 12 months

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Secondary Outcomes

Description: Will be summarized by group and time point. Associations between endpoints and demographic, treatment-related and resilience variables, as well as differences among groups will be assessed by t-test, analysis of variance or Chi-square test. Non-parametric tests (Wilcoxon rank sum, Kruskal-Wallis, Fisher's exact) will be employed when appropriate. Regression models (e.g., linear, logistic etc.) will also be employed. Change from baseline to subsequent time points in Likert scores will be modeled by mixed-effect models, while blocking on patient to control for repeated measures. Models will include baseline demographic, treatment-related, and resilience factor variables as covariates.

Measure: Survey responses

Time: At baseline, 6 months, and 12 months

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Description: Will be summarized by group and time point. Associations between endpoints and demographic, treatment-related and resilience variables, as well as differences among groups will be assessed by t-test, analysis of variance or Chi-square test. Non-parametric tests (Wilcoxon rank sum, Kruskal-Wallis, Fisher's exact) will be employed when appropriate. Regression models (e.g., linear, logistic etc.) will also be employed. Change from baseline to subsequent time points in Likert scores will be modeled by mixed-effect models, while blocking on patient to control for repeated measures. Models will include baseline demographic, treatment-related, and resilience factor variables as covariates.

Measure: Patient reported outcomes

Time: At baseline, 6 months, and 12 months

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Description: Will be summarized by group and time point. Associations between endpoints and demographic, treatment-related and resilience variables, as well as differences among groups will be assessed by t-test, analysis of variance or Chi-square test. Non-parametric tests (Wilcoxon rank sum, Kruskal-Wallis, Fisher's exact) will be employed when appropriate. Regression models (e.g., linear, logistic etc.) will also be employed. Change from baseline to subsequent time points in Likert scores will be modeled by mixed-effect models, while blocking on patient to control for repeated measures. Models will include baseline demographic, treatment-related, and resilience factor variables as covariates.

Measure: Changes of survey responses

Time: At baseline, 6 months, and 12 months

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Description: Will be summarized by group and time point. Associations between endpoints and demographic, treatment-related and resilience variables, as well as differences among groups will be assessed by t-test, analysis of variance or Chi-square test. Non-parametric tests (Wilcoxon rank sum, Kruskal-Wallis, Fisher's exact) will be employed when appropriate. Regression models (e.g., linear, logistic etc.) will also be employed. Change from baseline to subsequent time points in Likert scores will be modeled by mixed-effect models, while blocking on patient to control for repeated measures. Models will include baseline demographic, treatment-related, and resilience factor variables as covariates.

Measure: Changes in discrete responses

Time: At baseline, 6 months, and 12 months

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Description: Will be separately modeled by logistic regression with relation to group and time point as well as demographic and cancer characteristics in order to assess factors associated with non-response and to assess associated bias. Other statistical approaches might be used as appropriate.

Measure: Incidence of survey question non-response

Time: At baseline, 6 months, and 12 months

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Primary Outcomes

Description: The primary endpoint, ctDNA detection rate, overall and within different cancer types will be presented as a proportion of patients with a positive ctDNA test out of those tested, with 90% confidence intervals

Measure: ctDNA detection rate within different cancer types (and overall)

Time: Throughout study completion, up to one year

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Secondary Outcomes

Description: All secondary endpoints will be analysed in the patients diagnosed with suspected cancer, i.e. positive ctDNA result, unless stated. They will also be presented overall and by cancer type. The proportion of patients with positive ctDNA result which identified a diagnosis and/or commenced treatment will be presented as a proportion with 90% confidence intervals

Measure: Proportion of patients with a positive ctDNA result which identified a diagnosis and/or commenced treatment

Time: Throughout study completion, up to one year

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Description: Proportion of patients with positive ctDNA result which assisted in prioritising invasive diagnostic tests will be presented as a proportion with 90% confidence intervals

Measure: Proportion of patients with a positive ctDNA result which assisted in prioritising invasive diagnostic tests

Time: Throughout study completion, up to one year

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Description: The association between ctDNA result (positive versus negative) and the PREVAIL-imaging pathway scoring result will be assessed descriptively by presenting cross-tabulations and relevant proportions

Measure: The association of ctDNA result (positive versus negative) and the PREVAIL-imaging pathway scoring result

Time: Throughout study completion, up to one year

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Description: Simple estimation of the cost of liquid biopsy in lieu of tissue biopsy as compared to standard of care investigations and treatments prioritisation will be performed

Measure: Estimation of the cost of liquid biopsy in lieu of tissue biopsy as compared to standard of care investigations and treatments prioritisation

Time: Throughout study completion, up to one year

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Primary Outcomes

Description: To prospectively assess HRQOL in adult patients with hematologic malignancies, overall and by patient subgroups (e.g., by diagnosis of COVID-19)

Measure: HRQOL in adult patients with hematologic malignancies

Time: After 2 years from date of registration

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Description: To prospectively assess symptoms in adult patients with hematologic malignancies, overall and by patient subgroups (e.g., by diagnosis of COVID-19)

Measure: Symptoms in adult patients with hematologic malignancies

Time: After 2 years from date of registration

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Description: To prospectively assess adherence to therapy in adult patients with hematologic malignancies, overall and by patient subgroups (e.g., by diagnosis of COVID-19)

Measure: Adherence to therapy in adult patients with hematologic malignancies

Time: After 2 years from date of registration

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Secondary Outcomes

Description: To describe the prevalence of clinically relevant functional limitations (e.g., physical and social) and symptoms (e.g., fatigue, pain and dyspnea) by type of hematologic malignancy and by type of treatment (e.g., standard chemotherapy of oral anticancer therapies)

Measure: Prevalence of clinically relevant functional limitations and symptoms

Time: After 2 years from date of registration

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Description: To investigate factors associated with physical and mental health concerns

Measure: Factors associated with physical and mental health concerns

Time: After 2 years from date of registration

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Description: To examine the financial and social impact imposed by the COVID-19 pandemic on patient health outcomes

Measure: Financial and social impact imposed by the COVID-19 pandemic on patient health outcomes

Time: After 2 years from date of registration

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Description: To examine the limitations in accessing routine medical care services imposed by the COVID-19 pandemic on patient health outcomes

Measure: Limitations in accessing routine medical care services imposed by the COVID-19 pandemic on patient health outcomes

Time: After 2 years from date of registration

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Description: To describe clinical strategies adopted by physicians in response to patient-generated alerts, across different clinical scenarios

Measure: Clinical strategies adopted by physicians

Time: After 2 years from date of registration

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Primary Outcomes

Measure: Subject incidence of Dose-limiting toxicities (DLT)

Time: through out the DLT period, approximately 21 days

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Measure: Number of subjects participants with adverse events

Time: Through study completion, approximately 3 years

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Measure: Plasma concentration of D-1553 as a single agent or in combination with other therapies in subjects wiht advanced or metastatic solid tumors with KRas G12C mutation.

Time: Through study completion, approximately 3 years

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Primary Outcomes

Description: Deep venous thrombosis and/or pulmonary embolism.

Measure: Rate of venous thromboembolism

Time: From Day 9 to Day 42

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Secondary Outcomes

Description: Rate of hospitalization

Measure: Hospitalization due to venous thromboembolism

Time: Day 23

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Description: Time between the date of inclusion and the date of death for any reason.

Measure: Overall Survival

Time: Day 23

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Description: Time between the date of inclusion and the date of death for venous thromboembolism.

Measure: Specific survival

Time: Day 23

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Description: Common toxicity criteria from the NCI CTCAE V5.0

Measure: Safety profile using the common toxicity criteria from the NCI CTCAE V5.0

Time: Day 1 to Day 23

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Description: Khorana score (low risk (score=0), medium risk (score=1 ou 2) and high risk (score ≥ 3)

Measure: Predictive factors for venous thromboembolism

Time: Day 1 to Day 23

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Description: Caprini score (very low risk (score=0), low risk (score=1 or 2), medium risk (score=3 or 4)and high risk (score ≥ 5)

Measure: Predictive factors for venous thromboembolism

Time: Day 1 to Day 23

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Description: Common toxicity criteria from the NCI CTCAE V5.0

Measure: rate of symptomatic venous thromboembolism between the COVID-19 negative and COVID-19 positive patients

Time: Day 1 to Day 23

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Primary Outcomes

Description: Number of treatment emergent adverse events as assessed by CTCAE v5.0

Measure: Incidence and severity of Treatment Emergent Adverse Events by CTCAE v5.0

Time: From screening to end of study (approximately up to 2 years) for each patient

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Description: Incidence of DLTs

Measure: To characterize dose-limiting toxicities (DLTs)

Time: DLT evaluation period is through cycle 1 (21 days)

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Secondary Outcomes

Description: Study drug concentration

Measure: To characterize study drug concentration

Time: There are 9 blood draw collection time points at Cycles 1 and 3, 3 blood draw time points at Cycles 2,4,5 and 6, and collection at every 3 cycles after cycle 6 until end of study (approximately up to 2 years). Each cycle is 21 days.

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Description: Anti-drug antibody

Measure: To measure the concentration of anti-drug antibody

Time: There are 2 collection time points at Cycles 1 and 3, 1 collection time point at Cycles 2, 4, 5 and 6, and and collection at every 3 cycles after cycle 6 until end of study (approximately up to 2 years). Each cycle is 21 days.

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Primary Outcomes

Description: Patient's perspective on telemedicine on a Likert Scale

Measure: Patient's perspective on telemedicine on a Likert Scale

Time: Through survey completion, an average of 15 minutes

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Primary Outcomes

Description: The PROMIS Anxiety Short form consists of 2 items addressing patient anxiety with item response scores ranging from 1 (never) to 5 (Always). Raw scores are converted to scaled T-scores with higher scores indicating a greater level of anxiety. Significant changes over time and trends in patient reported outcomes will be analyzed via student's T-test.

Measure: Changes in the Patient Reported Outcome Measurement Information System (PROMIS) Anxiety Short Form over time

Time: Baseline, Week 9, and Week 15, up to 15 weeks total

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Description: The PROMIS Depression Short form consists of 4 items addressing patient depression with item response scores ranging from 1 (never) to 5 (Always). Raw scores are converted to scaled T-scores with higher scores indicating a greater level of depression. Significant changes over time and trends in patient reported outcomes will be analyzed via student's T-test.

Measure: Changes in the Patient Reported Outcome Measurement Information System (PROMIS) Depression Short Form over time

Time: Baseline, Week 9, and Week 15, up to 15 weeks total

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Description: The FACT-G is a 27-item questionnaire designed to measure four domains of health related quality of life (HRQOL) in cancer patients with 4 domains of interest: Physical, social, emotional, and functional well-being. Each tem response score ranges from 0 (not at all) to 5 (very much). The total score is a sum of the subscale scores, with a range from 0 - 108. The higher the score, the better the HRQOL.

Measure: Changes in the Functional Assessment of Cancer Therapy (FACT-G) scores

Time: Baseline, Week 9, and Week 15, up to 15 weeks total

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Primary Outcomes

Description: The Bayesian optimal interval (BOIN) design will be used to find the MTD based on safety.

Measure: Maximum tolerated dose (MTD)

Time: Up to 21 days

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Description: Defined by Common Terminology Criteria for Adverse Events version 5.0. Will be summarized by frequency and magnitude.

Measure: Grade 3/4 adverse event rate

Time: Up to 30 days

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Description: The proportion of participants who receive 3 or more cycles of the combination, will be calculated with a 90% confidence interval.

Measure: Number of cycles received of the combination of entinostat, atezolizumab, carboplatin, and etoposide

Time: Up to cycle 4 (1 cycle = 21 days)

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Secondary Outcomes

Description: Defined as the proportion of patients alive and without disease progression after 9 months from study enrollment. The 9 month PFS rate will be estimated with a 90% confidence interval. The Kaplan Meier estimator will be used to estimate survival curves.

Measure: 9-month progression free survival (PFS) rate

Time: 9 months

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Primary Outcomes

Description: Godin Leisure-Time Exercise Questionnaire

Measure: Physical Activity

Time: 14 days

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Description: COVID-19 Pandemic Psychosocial Functioning Measure

Measure: Psychosocial Function during COVID-19

Time: 14 days

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Secondary Outcomes

Description: The Exercise Self-efficacy Scale will be used to measure confidence in ability to exercise. A higher score indicated a higher confidence.

Measure: Self-Efficacy

Time: 14 days

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Description: The Pittsburgh Sleep Quality Index will be used to measure sleep quality and disturbances. A higher score indicates a higher sleep disturbance.

Measure: Sleep Quality

Time: 14 days

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Description: The Functional Assessment in Chronic Illness Therapy - Fatigue (FACIT-F) will be used to measure fatigue as well. Higher scores indicate less fatigue.

Measure: Fatigue

Time: 14 days

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Description: The Hospital Anxiety and Depression Scale (HADS) will be used to produce an anxiety score. Higher scores indicate higher symptoms of anxiety.

Measure: Anxiety

Time: 14 days

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Description: The Hospital Anxiety and Depression Scale (HADS) will be used to produce an anxiety score. Higher scores indicate higher symptoms of depression.

Measure: Depression

Time: 14 days

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Description: The UCLA Loneliness Scale will be used to measure feelings of loneliness and isolation. Higher scores indicate higher degrees of loneliness.

Measure: Loneliness

Time: 14 days

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Description: The Rosenberg Self-Esteem Scale (RSE) will be used to measure global self-esteem. Items are used to calculate an esteem score, higher scores are indicative of higher esteem.

Measure: Global Self-Esteem

Time: 14 days

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Description: The Functional Assessment in Cancer Therapy- Cognition (FACT-Cog) measures levels of cognitive impairment, quality of life and perceived cognitive ability. Items are summed up to calculate scores from each subsection.

Measure: Subjective Cognitive Impairment

Time: 14 days

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Description: The Social Support of Exercise scale is aimed to assess the degree in which family and friends demonstrate support for exercise behavior. Higher scores indicate a higher level of support.

Measure: Social Support

Time: 14 days

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Description: The Satisfaction of Life Scale (SWLS) is developed to assess global satisfaction is various age groups.

Measure: Satisfaction of Life

Time: 14 days

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Description: The Perceived Stress Scale is a 10-item scale developed to measure the perceptions of a person's stress.

Measure: Stress

Time: 14 days

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Description: A qualitative interview will be performed to measure the perceptions and barriers of exercise during the COVID-19 pandemic. This interview is comprised of items designed by the research team.

Measure: Perceptions of Exercise

Time: up to one month after enrollment

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Primary Outcomes

Description: Investigator report; efficacy rule

Measure: Morphologic complete response rate of ADCT-301

Time: End of Study, up to 3 years

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Description: Number of adverse events as measured by self report

Measure: Safety of ADCT-301

Time: up to 12 weeks (84 days) after the last dose

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Primary Outcomes

Description: DLTs at each Phase I dose level will be reported. Pharmacokinetic analysis will be conducted using non-compartmental methods. All patients will be evaluable for toxicity from the time of their first treatment with AZA/ Bintrafusp alfa. Dose limiting toxicities will be assessed during the first 3 cycles of AZA/ Bintrafusp alfa therapy. Patients who have measurable disease present at baseline, have received at least 9 weeks of AZA/Bintrafusp alfa therapy (three cycles), and have had their disease re-evaluated will be considered evaluable for response.

Measure: Phase I: Determine pharmacokinetics, toxicities, maximum tolerated dose and recommended Phase 2 dose (RP2D) of aerosolized AZA in patients receiving IV Bintrafusp alfa for unresectable pulmonary metastases

Time: baseline, first treatment, end of each course

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Description: Patients who have measurable disease present at baseline, have received at least 9 weeks of AZA/Bintrafusp alfa therapy (three cycles), and have had their disease re-evaluated will be considered evaluable for response provided.

Measure: Phase II: Determine frequency of intrathoracic objective clinical response in patients with unresectable pulmonary metastases following administration of aerosolized AZA at the RP2D and IV Bintrafusp alfa

Time: baseline, end of each course

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Primary Outcomes

Description: evaluation via questionnaire

Measure: Influence of the COVID-19 pandemic on cancer patient's daily life

Time: single time

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Primary Outcomes

Description: We will use the COVID-19 Specific questionnaire. This scale will ask 15 questions that are organized into three sections: (a) Questions specific to the COVID-19 pandemic such as testing, serostatus, risk factors, loss of family or friends, isolation; (b) Thoughts, experiences and emotions regarding the COVID-19 pandemic; and (c) Health-related quality of life. This assessment was developed by Lorenzo Cohen (MD Anderson), in collaboration with investigators from the University of Miami and UCLA and is a comprehensive assessment of COVID-19 experiences.

Measure: Health-related quality of life and coronavirus disease 2019 (COVID-19)-specific domains of interest

Time: through study completion, an average of 6 months

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Description: Will evaluate bivariate associations between COVID-19 experiences and COVID-19-specific distress, HRQOL and clinical outcomes, using Pearson product-moment correlation coefficients, chi-squared tests, or analyses of variance (ANOVA) where appropriate.

Measure: COVID-19 experiences and COVID-19 specific distress

Time: through study completion, an average of 6 months

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Description: Will use linear regression (or generalized linear models, as applicable) to assess differences in the outcomes of interest between neuropathic pain patients who received neurofeedback (NFB) from either of the two NFB trials (principal investigator [PI]: Dr. Prinsloo) and the neuropathic pain patients who participated in Dr. Gibby-Reyes' trial (who, consequently, did not receive NFB).

Measure: Differences in outcomes between neuropathic pain patients

Time: through study completion, an average of 6 months

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Description: Will preliminarily test the interaction effect between each of the coping and resilience factors and COVID-19 experiences on COVID-19-specific distress, HRQOL and clinical outcomes.

Measure: Coping and resilience factors

Time: through study completion, an average of 6 months

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Primary Outcomes

Description: sum score on the Patient Health Questionnaire, a 9-item scale with a sumscore ranging between 0 and 27, with a higher score indicating more-severe depression.

Measure: Patient-reported severity of depression

Time: Baseline

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Description: sum score on the generalized anxiety disorder questionnaire, a 7-item scale with sumscore range between 0 and 21. A higher score indicates higher severity of anxiety.

Measure: Patient-reported severity of anxiety

Time: Baseline

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Description: score on the National Comprehensive Cancer Network Distress Thermometer, a one-item 0-10 scale. A higher score indicates higher distress.

Measure: Patient-reported severity of distress

Time: Baseline

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Secondary Outcomes

Description: Physical symptoms are assessed with individual-item response on the Edmonton Symptom Assessment Scale by the clinic. The ESAS includes 6 somatic symptom items, each of which is to be rated on a 0-10 scale, with higher scores indicating higher severity of the symptom.

Measure: Patient-reported physical symptoms

Time: Baseline

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Description: Substance use is documented by the treating physician and will be abstracted from clinic notes.

Measure: Substance use

Time: Baseline

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Description: Assessed using the brief COPE questionnaire. Will examine active versus avoidant coping. Active coping, planning, positive reframing, acceptance, humor, religion, emotional support-seeking, and instrumental support-seeking will be considered active coping strategies. Self-distraction, denial, venting, substance use, behavioral disengagement, and self-blame will be considered maladaptive coping strategies.

Measure: Patient-reported coping strategy

Time: Baseline

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Description: The Apathy evaluation Scale is an 18-item scale with a sum score ranging between 18 and 72. A higher scores indicates higher apathy..

Measure: Patient-reported levels of apathy

Time: Baseline

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Description: Patients indicate how often during the pandemic they engaged in the following 5 behaviors endorsed by the World Health Organization to decrease the transmission of coronavirus disease 2019 (COVID-19): washing hands regularly for 20 seconds with soap and water or alcohol-based hand rub, covering nose and mouth with a disposable tissue or flexed elbow when you cough or sneeze, avoiding close contact with people who are unwell, staying home and self-isolating from others in the household when feeling unwell, avoiding touching eyes, nose, and mouth when hands are unclean. The behaviors will be assessed on a Likert scale of 1-5, with 1 being "never" and 5 being "always". A not available (N/A) option will be given for staying home and self-isolating from others when feeling unwell, since participants may not experience a period of feeling unwell.

Measure: Patient-reported engagement in the 5 health behaviors endorsed by World Health Organization intended to curb the spread of the coronavirus

Time: Baseline

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Primary Outcomes

Description: Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)

Measure: Recommended phase 2 dose (RP2D) for NL-201

Time: Up to Day 33

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Description: Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)

Measure: Recommended dose schedule for NL-201

Time: Up to Day 33

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Description: Rate of adverse events in patients with advanced solid tumors

Measure: Incidence of treatment-emergent adverse events

Time: Up to Day 33

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Description: Rate of adverse event grades in patients with advanced solid tumors

Measure: Severity of treatment-emergent adverse events

Time: Up to Day 33

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Secondary Outcomes

Description: Based on Investigator assessment of radiographic imaging

Measure: Best Objective Response according to RECIST version 1.1

Time: Up to 36 months

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Description: Based on Investigator assessment of radiographic imaging

Measure: Objective Response Rate (ORR) according to RECIST version 1.1

Time: Up to 36 months

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Description: Based on Investigator assessment of radiographic imaging

Measure: Progression-Free Survival (PFS) according to RECIST version 1.1

Time: Up to 36 months

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Description: Based on Investigator assessment of radiographic imaging

Measure: Duration of Response (DOR) according to RECIST version 1.1

Time: Upto 36 months

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Description: Prespecified timepoints in serum before and after dosing with NL-201.

Measure: Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2)

Time: Up to 24 Months

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Description: Prespecified timepoints in serum before and after dosing with NL-201.

Measure: Pharmacokinetic (PK) profile of NL-201 by area under the plasma concentration time curve (AUC)

Time: Up to 24 months

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Description: Prespecified timepoints in serum before and after dosing with NL-201.

Measure: Pharmacokinetic (PK) profile of NL-201 by maximum observed plasma concentration (Cmax)

Time: Up to 24 months

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Description: Prespecified timepoints in serum before and after dosing with NL-201.

Measure: Pharmacokinetic (PK) profile of NL-201 by volume of distribution (Vd)

Time: Up to 24 Months

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Description: Anti-drug antibodies in serum during and after treatment with NL-201

Measure: Immunogenicity of NL-201

Time: Up to 24 months

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Other Outcomes

Description: Based on appropriate assay

Measure: Flow cytometry analysis of immune cells in blood

Time: Up to 36 months

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Description: Based on appropriate assay

Measure: Serum measurements of inflammatory cytokine levels

Time: Up to 36 months

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Description: Based on appropriate assay

Measure: Analysis of immune characteristics of the tumor microenvironment

Time: Up to 36 months

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Description: Based on Investigator assessment of imaging

Measure: Estimate additional measures of anti-tumor activity of NL- 201 per iRECIST criteria

Time: Up to 36 months

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