SNPMiner Trials by Shray Alag

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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation G12D

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 12 clinical trials

Clinical Trials


1 Pilot Study Of Safety And Feasibility Of GI-4000, An Inactivated Recombinant Saccharomyces Cerevisiae Expressing Mutant Ras Protein Combined With Adoptive Transfer And Chemoradiation in Locally Advanced Pancreatic Cancer

The purpose of this study is to determine if it is safe to add multiple immunotherapies to standard chemotherapy and radiation for treating pancreatic cancer tumors that cannot be completely removed by surgery. 1. GI-4000 Vaccination: The first involves a "vaccine," which is an injection (shot) that teaches your immune system to attack foreign invaders. The vaccine we will use is called "GI-4000" - a vaccine composed of yeast that is made to carry the same proteins (called "mutated Ras proteins") found in some pancreatic cancer cells. 2. Adoptive T-cell Transfer: The second type of immunotherapy in this study is called "adoptive T-cell transfer." This involves collecting a specific type of white blood cells from you (called "T-cells")and growing T-cells grown in a lab which may help the research participants' immune systems recover more quickly after chemotherapy, and possibly improved response to other immunotherapies. We hope that studying these agents together will teach us how to help the immune system fight pancreatic cancer.

NCT00837135
Conditions
  1. Pancreatic Cancer
Interventions
  1. Other: Screening
  2. Biological: GI-4000 Vaccine
  3. Biological: GI-4000 Vaccine + Activated T Cells
  4. Biological: Surgical Evaluation after Vaccine #4
MeSH:Pancreatic Neoplasms
HPO:Neoplasm of the pancreas

1. Histologically-confirmed pancreatic adenocarcinoma that expresses one of the GI-4000-related k-ras oncoproteins (G12V, G12C, G12D, Q61L, or Q61R) 2. Locally advanced disease, (stages I-III, i.e no evidence of metastasis outside the pancreas and its regional lymph nodes). --- G12V --- --- G12C --- --- G12D ---

Primary Outcomes

Measure: To evaluate the feasibility of incorporating GI-4000 vaccine and activated T-cell infusion into a regimen of chemotherapy, radiation, and surgical resection to treat locally advanced pancreatic cancer.

Time: 1 year

2 Phase I - Escalating Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Locally Advanced Adenocarcinoma of the Pancreas, and a Single Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Non-operable Adenocarcinoma of the Pancreas

Phase 0 - Open label, Single dose study of siG12D LODER in Patients with operable adenocarcinoma of the pancreas. The primary endpoint: To assess efficacy and local distribution of siRNA out of eight high dose siG12D LODERs in patients diagnosed with operable adenocarcinoma of the pancreas. The Secondary endpoint: Short term tolerability and safety assessment Phase I - This study is designed to investigate the safety of siG12D LODER (Local Drug EluteR) in patients diagnosed with adenocarcinoma of the pancreas. The primary endpoint: To asses efficacy of siG12D LODER and local distribution in non-operable patients by histopathology measurements, local distribution by RNA analysis. To define the dose-limiting toxicities (DLT) The Secondary endpoint 1. To determine the recommended Phase II dose (RP2D) 2. To define and maximum tolerated dose (MTD) 3. In the event of surgery, assessment of siG12D LODER local distribution and efficacy will be based on histopathology measurements and RNA analysis. 4. Progression free survival - only by long term follow-up

NCT01188785
Conditions
  1. Pancreatic Ductal Adenocarcinoma
  2. Pancreatic Cancer
Interventions
  1. Drug: siG12D LODER
MeSH:Adenocarcinoma Pancreatic Neoplasms
HPO:Neoplasm of the pancreas

The majority of pancreatic ductal adenocarcinomas involve mutations in the KRAS oncogene (the most common is G12D), therefore stable administration of KRASG12D siRNA has the potential to silence and lead to apoptosis of such cancer cells and thereby slow and even halt the tumor growth. --- G12D ---

Primary Outcomes

Measure: Number of Participants with Adverse Events

Time: Phase 0 - 6 weeks, Phase I - 2 months

3 A Phase 2 Trial of Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D

The purpose of this study is to test the drug Bortezomib to see how well it works. The investigators want to find out what effects, good or bad, it has on patients with a limited smoking history or who have a specific mutation associated with their lung cancer.

NCT01833143
Conditions
  1. Non-Small Cell Lung Cancer
Interventions
  1. Drug: Bortezomib
  2. Drug: Acyclovir
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

A Phase 2 Trial of Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D. --- G12D ---

Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D The purpose of this study is to test the drug Bortezomib to see how well it works. --- G12D ---

Inclusion Criteria: - Pathologic or cytologic evidence of non-small cell lung cancer (NSCLC) - Documented KRAS mutation - History of smoking < 100 cigarettes (never-smoker) OR patient with a KRAS G12D mutation regardless of smoking history - Clinical stage IIIB/IV or recurrent/medically inoperable NSCLC - Age ≥ 18 years - Three (3) weeks since last chemotherapy, and three (3) weeks since prior radiation therapy and recovered from treatment - Karnofsky performance status ≥ 70% - Adequate hematologic, and/or hepatic function WBC ≥ 3,000/ul or absolute neutrophil count ≥ 1,000/ul Hemoglobin ≥ 9.0 g/dl Platelet count ≥ 100,000/ul AST ≤ 2.0 X ULN (upper limit of normal) - Total bilirubin ≤1.5 x ULN Measurable indicator lesions by RECIST v1.1 criteria. --- G12D ---

- No active concurrent malignancy, with the exception of in-situ malignancy completely resected basal cell carcinoma or squamous cell carcinomas of the skin low-risk prostate cancer after curative therapy - Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial Inclusion Criteria: - Pathologic or cytologic evidence of non-small cell lung cancer (NSCLC) - Documented KRAS mutation - History of smoking < 100 cigarettes (never-smoker) OR patient with a KRAS G12D mutation regardless of smoking history - Clinical stage IIIB/IV or recurrent/medically inoperable NSCLC - Age ≥ 18 years - Three (3) weeks since last chemotherapy, and three (3) weeks since prior radiation therapy and recovered from treatment - Karnofsky performance status ≥ 70% - Adequate hematologic, and/or hepatic function WBC ≥ 3,000/ul or absolute neutrophil count ≥ 1,000/ul Hemoglobin ≥ 9.0 g/dl Platelet count ≥ 100,000/ul AST ≤ 2.0 X ULN (upper limit of normal) - Total bilirubin ≤1.5 x ULN Measurable indicator lesions by RECIST v1.1 criteria. --- G12D ---

Primary Outcomes

Description: The following evaluations will be conducted to assess the efficacy of bortezomib - radiographic response rate by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Measure: Radiographic Response Rate

Time: 2 years

Secondary Outcomes

Description: Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Measure: Progression Free Survival

Time: 2 years

Description: Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE v4.0,).

Measure: Participants Evaluated for Toxicity

Time: 2 years

Measure: Overall Survival

Time: 2 years

4 Chemotherapy in KRAS Mutated Chemotherapy Naive Non-small Cell Lung Cancer Patients: a Phase III Study Comparing Cisplatin-pemetrexed With Carboplatin-paclitaxel-bevacizumab: NVALT 22

The purpose of this study is to determine whether carboplatin-paclitaxel-bevacizumab results in a prolonged progression free survival compared to cisplatin-pemetrexed as first line treatment in patients with KRAS mutated non-small cell lung cancer.

NCT02743923
Conditions
  1. Carcinoma, Non-Small Cell Lung
Interventions
  1. Drug: carboplatin
  2. Drug: paclitaxel
  3. Drug: Bevacizumab
  4. Drug: Pemetrexed
  5. Drug: cisplatin
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

The two most common KRAS types are G12C in about 40% of cases, G12V in 18% and G12D in 15% of cases. --- G12C --- --- G12V --- --- G12D ---

Primary Outcomes

Measure: progression free survival

Time: Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months

Secondary Outcomes

Measure: disease control rate

Time: Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months.

Description: Stratification for KRAS mutation (G12V versus G12C versus other)

Measure: overall survival

Time: date of randomization to the date of death from any cause, assessed up to 60 months.

Description: The two most common KRAS types are G12C in about 40% of cases, G12V in 18% and G12D in 15% of cases. Subgroup analyses are planned to explore treatment effect in these different KRAS mutations groups. At baseline the metastatic patterns of these subgroups will be described. KRAS mutations in NSCLC occur mainly in codon 12 and 13. Stratification for KRAS mutation (G12V versus G12C versus other) at randomization.

Measure: outcome between G12V versus G12C versus other subtypes of KRAS mutations (mutational analysis on plasma and blood platelets).

Time: date of randomization to the date of death from any cause, assessed up to 60 months.

Measure: response by Crabb criteria (if applicable)

Time: Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months

5 Comparison of KRAS/BRAF Mutational Status Between Tumor Tissue Section Analysis With Conventional Techniques and Plasma Samples Analysis (KPLEX2)

The goal of this multicenter prospective study is to validate, and ultimately translate in routine clinical practice, the use of plasma analysis of ccfDNA for the determination of KRAS mutation status in mCRC patients.

NCT02784639
Conditions
  1. Colorectal Cancer
Interventions
  1. Other: Plasma Analysis of circulating cell free DNA
  2. Other: Tumor tissue analysis of circulating cell free DNA
MeSH:Colorectal Neoplasms
HPO:Neoplasm of the large intestine

As a consequence, the method was adapted to detect the six more frequent KRAS mutations in CRC (G12D, G12V, G13D, G12S, G12C, G12A) and the BRAF V600E. --- G12D ---

Primary Outcomes

Description: Area under the ROC curve of the mutation percentage obtained from plasma ccfDNA analysis

Measure: Area under ROC curve

Time: 12 month

6 Pilot Study of Mature Dendritic Cell Vaccination Against Mutated KRAS in Patients With Resectable Pancreatic Cancer

This research study is designed to evaluate the effects of a dendritic cell (kind of white blood cell) vaccine for pancreatic cancer.

NCT03592888
Conditions
  1. Pancreatic Ductal Adenocarcinoma
Interventions
  1. Drug: mDC3/8-KRAS Vaccine
MeSH:Adenocarcinoma

Inclusion Criteria: - Pathologically-confirmed KRAS(G12D-), KRAS(G12V-), KRAS(G12R-) or KRAS(G12C-mutated) pancreatic ductal adenocarcinoma who are at high risk of relapse and have no evidence of disease. --- G12D ---

Primary Outcomes

Measure: Safety and side effects of vaccine per CTCAE 4.0

Time: At time of consent through 30 days after the subject's last DC vaccine

Secondary Outcomes

Measure: Immune response measuring increased numbers of peptide specific T cells as calculated by the peptide-MHC multimer assay.

Time: Day 1 through week 12

Measure: Disease Free Survival

Time: 30 days following second vaccine through study completion approximately 12 months after the first DC vaccine

7 A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients

Background: A new cancer therapy takes white blood cells from a person, grows them in a lab, genetically changes them, then gives them back to the person. Researchers think this may help attack tumors in people with certain cancers. It is called gene transfer using anti-KRAS G12D mTCR cells. Objective: To see if anti-KRAS G12D mTCR cells are safe and cause tumors to shrink. Eligibility: Adults ages 18-70 who have cancer with a molecule on the tumors that can be recognized by the study cells Design: Participants will be screened with medical history, physical exam, scans, photography, and heart, lung, and lab tests. An intravenous (IV) catheter will be placed in a large vein in the chest. Participants will have leukapheresis. Blood will be removed through a needle in an arm. A machine will divide the blood and collect white blood cells. The rest of the blood will be returned to the participant through a needle in the other arm. A few weeks later, participants will have a hospital stay. They will: - Get 2 chemotherapy medicines by IV over 5 days. - Get the changed cells through the catheter. Get up to 9 doses of a medicine to help the cells. They may get a shot to stimulate blood cells. - Recover in the hospital for up to 3 weeks. They will provide blood samples. Participants will take an antibiotic for at least 6 months. Participants will have several follow-up visits over 2 years. They will repeat most of the screening tests and may have leukapheresis. Participants blood will be collected for several years.

NCT03745326
Conditions
  1. Gastrointestinal Cancer
  2. Pancreatic Cancer
  3. Gastric Cancer
  4. Colon Cancer
  5. Rectal Cancer
Interventions
  1. Drug: Cyclophosphamide
  2. Drug: Fludarabine
  3. Drug: Aldesleukin
  4. Biological: anti-KRAS G12D mTCR PBL
MeSH:Gastrointestinal Neoplasms
HPO:Malignant gastrointestinal tract tumors Neoplasm of the gastrointestinal tract

A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients. --- G12D ---

Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients Background: A new cancer therapy takes white blood cells from a person, grows them in a lab, genetically changes them, then gives them back to the person. --- G12D ---

It is called gene transfer using anti-KRAS G12D mTCR cells. --- G12D ---

Objective: To see if anti-KRAS G12D mTCR cells are safe and cause tumors to shrink. --- G12D ---

-INCLUSION CRITIERIA: 1. Measurable (per RECIST v1.1 criteria), metastatic, or unresectable malignancy expressing G12D mutated KRAS as assessed by one of the following methods: RT-PCR on tumor tissue, tumor DNA sequencing, or any other CLIA-certified laboratory test on resected tissue. --- G12D ---

Patients shown to have tumors expressing G12D mutated NRAS and HRAS will also be eligible as these oncogenes share complete amino acid homology with G12D mutated KRAS for their first 80 N-terminal amino acids, completely encompassing the target epitope. --- G12D ---

Patients shown to have tumors expressing G12D mutated NRAS and HRAS will also be eligible as these oncogenes share complete amino acid homology with G12D mutated KRAS for their first 80 N-terminal amino acids, completely encompassing the target epitope. --- G12D --- --- G12D ---

Gastrointestinal Cancer Pancreatic Cancer Gastric Cancer Colon Cancer Rectal Cancer Gastrointestinal Neoplasms Background: - We generated an HLA-A11:01-restricted murine T-cell receptor (mTCR) that specifically recognizes the G12D-mutated variant of KRAS (and other RAS family genes) expressed by many human cancers and constructed a single retroviral vector that contains alpha and beta chains that confer recognition of this antigen when transduced into PBL. --- G12D ---

Objectives: -Primary objectives: - Phase I: Determine the safety of administering PBL transduced with anti-KRAS G12D mTCR in concert with preparative lymphodepletion and high-dose interleukin-2 (IL-2; aldesleukin). --- G12D ---

- Phase II: Determine if anti-KRAS G12D mTCR-transduced PBL can mediate the regression of tumors harboring the RAS G12D mutation. --- G12D ---

- Phase II: Determine if anti-KRAS G12D mTCR-transduced PBL can mediate the regression of tumors harboring the RAS G12D mutation. --- G12D --- --- G12D ---

Eligibility: - Patients must be/have: - Age greater than or equal to 18 years and less than or eqaul to 70 years - HLA-A*11:01 positive - Metastatic or unresectable RAS G12D-expressing cancer which has progressed after standard therapy (if available). --- G12D ---

Design: - This is a phase I/II, single center study of PBL transduced with anti-KRAS G12D mTCR in HLA-A*11:01 positive patients with advanced solid tumors expressing G12D mutated RAS. - PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth. --- G12D ---

Design: - This is a phase I/II, single center study of PBL transduced with anti-KRAS G12D mTCR in HLA-A*11:01 positive patients with advanced solid tumors expressing G12D mutated RAS. - PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth. --- G12D --- --- G12D ---

- Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-KRAS G12D mTCR. --- G12D ---

- On Day 0, patients will receive PBL transduced with the anti-KRAS G12D mTCR and will then begin high-dose aldesleukin. --- G12D ---

- The study will be conducted using a phase I/II Simon minimax design, with two separate cohorts for the Phase II component: Cohort 2a, patients with RAS G12D pancreatic cancer, and Cohort 2b, patients with RAS G12D non-pancreatic cancer. --- G12D ---

- The study will be conducted using a phase I/II Simon minimax design, with two separate cohorts for the Phase II component: Cohort 2a, patients with RAS G12D pancreatic cancer, and Cohort 2b, patients with RAS G12D non-pancreatic cancer. --- G12D --- --- G12D ---

Primary Outcomes

Description: Grade and type of toxicity per dose level; fraction of patients who experience a DLT at a given dose level, and number and grade of each type of DLT

Measure: Frequency and severity of treatment-related adverse events

Time: From time of cell infusion to two weeks after cell infusion

Description: Percentage of patients who have a clinical response (PR + CR) to treatment (objective tumor regression)

Measure: Response rate

Time: 6 weeks and 12 weeks following administration of the cell product, then every 3 months x3, then every 6 months x 2 years, then per PI discretion

8 A Phase 1, Open-Label, Multicenter Study to Assess the Safety and Tolerability of mRNA-5671/V941 as a Monotherapy and in Combination With Pembrolizumab in Participants With KRAS Mutant Advanced or Metastatic Non-Small Cell Lung Cancer, Colorectal Cancer or Pancreatic Adenocarcinoma

This study will determine the safety and tolerability and establish a preliminary recommended Phase 2 dose of V941(mRNA-5671/V941) as a monotherapy and in combination with pembrolizumab infusion.

NCT03948763
Conditions
  1. Neoplasms
  2. Carcinoma, Non-Small-Cell Lung
  3. Pancreatic Neoplasms
  4. Colorectal Neoplasms
Interventions
  1. Biological: V941
  2. Biological: Pembrolizumab
MeSH:Neoplasms Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Pancreatic Neoplasms
HPO:Neoplasm Neoplasm of the large intestine Neoplasm of the pancreas Non-small cell lung carcinoma

All - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor identified by local laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D ---

Primary Outcomes

Description: The following toxicities graded for severity using NCI Common Terminology for Adverse Events (CTCAE), Version 4.0 will be considered a DLT if judged by the investigator to be possibly related to study investigational products: 1) Grade 4 nonhematologic toxicity (ie. not a laboratory finding). 2) Grade 4 hematologic toxicity lasting ≥ 7 days, except thrombocytopenia: 3) Grade 4 thrombocytopenia of any duration 4) Grade 3 thrombocytopenia associated with clinically significant bleeding 5) Any nonhematologic AE ≥ Grade 3 in severity, with some exceptions 6) Any Grade 3 or Grade 4 nonhematologic laboratory value that meets one of the study criteria 7) Febrile neutropenia Grade 3 or Grade 4 8) Prolonged delay (> 2 weeks) in initiating Cycle 2 due to treatment-related toxicity. 9) Any treatment-related toxicity that causes the participant to discontinue treatment during Cycle 1. 10) Grade 5 toxicity 11) Any other clinically significant toxicity judged to be a DLT by the investigator.

Measure: Dose-Limiting Toxicities (DLTs)

Time: Cycle 1 (Up to 21 days)

Description: Number of participants who experienced an AE. An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Measure: Adverse Events (AEs)

Time: Up to approximately 25 months

Description: Number of participants who discontinued from study due to an AE. An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Measure: Discontinuations

Time: Up to approximately 24 months

Secondary Outcomes

Description: ORR is assessed by the investigator based on Response Rate Assessed by Modified Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and RECIST for immune-based therapeutics (iRECIST) following administration of V941 in combination with pembrolizumab. Objective response is a confirmed complete response (CR) or partial response (PR).

Measure: Objective Response Rate (ORR)

Time: Up to approximately 24 months

Description: Presence of and changes in the quantity of mutant KRAS specific T cells in the blood.

Measure: Mutant KRAS Specific T cells

Time: Up to approximately 24 months

Other Outcomes

Description: T-cell receptor (TCR) clonality and diversity in the periphery and tumor.

Measure: T-cell receptor (TCR)

Time: Up to approximately 24 months

9 Clinical Trial Evaluating the Safety and Activity of Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer

This clinical trial will evaluate the safety and activity of mutant KRAS G12V-specific TCR transduced T cell therapy for advanced pancreatic cancer patients who express the KRAS G12V mutation and HLA-A*11:01 allele. The theoretical basis of this study is that mutant KRAS antigen-specific TCR transduced autologous Tcells will target and kill HLA-matched mutant KRAS cancer cells but not normal cells.

NCT04146298
Conditions
  1. Pancreatic Cancer
  2. Pancreatic Neoplasms
  3. Pancreatic Ductal Adenocarcinoma
  4. Advanced Cancer
Interventions
  1. Drug: Cyclophosphamide
  2. Drug: Fludarabine
  3. Biological: Mutant KRAS G12V-specific TCR transduced autologous T cells
  4. Drug: Anti-PD-1 monoclonal antibody
MeSH:Pancreatic Neoplasms
HPO:Neoplasm of the pancreas

For example, TCRs that target mutant KRAS G12D peptides presented by HLA-C*08:02, and a TCR that targets a KRAS G12V peptide presented by HLA-A*11:01 have been identified. --- G12D ---

Mutant KRAS-reactive T cells appear capable of inducing tumor regression as highlighted in a patient with metastatic colorectal cancer who experienced regression of metastatic tumors after infusion of HLA-C*08:02-restricted KRAS-G12D reactive tumor-infiltrating lymphocytes (TIL). --- G12D ---

Primary Outcomes

Description: Aggregate of all adverse events, as well as their frequency and severity

Measure: Frequency and severity of treatment-related adverse events

Time: 2 years following cell infusion

Description: Percentage of patients who have a clinical response to treatment (objective tumor regression)

Measure: Objective response rate

Time: From the date of cell infusion to disease progression (up to 24 months after cell infusion).

Secondary Outcomes

Description: The percentage of TCR transduced T cells in peripheral blood will be detected with an established flow cytometric assay.

Measure: The percentage of TCR transduced T cells in peripheral blood

Time: 2, 6 and 12 weeks after cell infusion, then every 3 months, and up to 24 months after cell infusion.

Description: The time between cell infusion and the death of patients

Measure: Overall survival

Time: From date of cell infusion until the date of death from any cause, whichever came first, assessed up to 24 months after cell infusion.

10 A Phase 1, Open Label, Dose Escalation Study of RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors

This study is a multi-center, open-label, dose escalation study of RLY-1971 in subjects with advanced or metastatic solid tumors.

NCT04252339
Conditions
  1. Solid Tumor, Unspecified, Adult
Interventions
  1. Drug: RLY-1971
MeSH:Neoplasms
HPO:Neoplasm

Male and female subjects of child-bearing potential are willing to use medically acceptable methods of birth control from the screening visit through 30 days after the last dose of study medication Exclusion Criteria: 1. Subjects with documented history of tumor mutations that may not be amenable to treatment with RLY-1971, including 1. KRAS mutations: G12D, G12V, G13X, and Q61X 2. BRAF V600E mutation 3. MEK mutations 2. Subjects with prior antineoplastic therapy within 3 weeks of Study Day 1, or 5 half-lives, whichever is shorter 3. Subjects with prior palliative radiotherapy within 1 week of Study Day 1 4. Subjects who have had major surgery or trauma, or incomplete recovery from surgery or trauma, within 4 weeks of Study Day 1 5. Subjects with known central nervous system (CNS) primary tumor, uncontrolled CNS metastases, or carcinomatous meningitis. --- G12D ---

Primary Outcomes

Measure: Maximum Tolerated Dose (MTD)

Time: Escalation Phase - 18 month Enrollment

Measure: Recommended Phase 2 Dose (RP2D)

Time: Escalation Phase - 18 month Enrollment

Secondary Outcomes

Description: Blood samples may be taken at pre-dose, 0.5, 1, 2, 4, 6, and 8hrs on Cycle I Day 1 and 15, 24 hrs post dose on Cycle 1 Day 2, 48hrs post dose on Cycle 1 Day 3, and post dose on Cycle 2 Day 1

Measure: Plasma concentration levels of RLY-1971

Time: At the beginning of Cycle 1 & Cycle 2 (Each Cycle is 21 days)

Description: Evaluation by RECIST 1.1; ORR is defined as the proportion of subjects in the response evaluable population who achieve the best overall response (BOR) of CR or PR

Measure: Objective Response Rate (ORR)

Time: Through study completion (an average of one year)

Description: DCR is defined as the percentage of response evaluable subjects who achieve a BOR of CR, PR or SD for at least 3 months

Measure: Disease Control Rate (DCR)

Time: Through study completion (an average of one year)

Other Outcomes

Description: Blood will be collected at pre-dose at baseline on Cycle 1, Day 1 (C1D1) and at 3 time points (pre-dose, 2 hours post-dose, and 4 hours post-dose) on Cycle 1, Day 15 (C1D15) to assess the extent of target engagement.

Measure: Changes in phospho-ERK levels

Time: At the beginning of Cycle 1 Day 1 post and pre

Description: Blood will be collected at screening and at End of Treatment on all patients

Measure: Tumor mutations by sequencing circulating tumor DNA (ctDNA)

Time: At the beginning of Cycle 1 Day 1

Description: DOR is defined as the time from the participant's initial objective response (CR or PR) to RLY-1971, to disease progression or death due to any cause, whichever occurs first

Measure: Duration of Response (DOR)

Time: Through study completion (an average of one year)

Description: TTR is defined as the period of time from the date of first the dose of RLY-1971 administration until the first objective documentation of response.

Measure: Time to Response (TTR)

Time: Through study completion (an average of one year)

Description: TTP is defined as the interval between the first dose of RLY-1971 until disease progression

Measure: Time to Progression (TTP)

Time: Through study completion (an average of one year)

Description: PFS is defined as the time from the start of study treatment to the first documented disease progression per RECIST v1.1, or death due to any cause, whichever occurs first

Measure: Progression-free Survival (PFS).

Time: Through study completion (an average of one year)

11 First-in-Human, Phase 1/1b, Open-label, Multicenter Study of Bifunctional EGFR/TGFβ Fusion Protein BCA101 Alone and in Combination With Pembrolizumab in Patients With EGFR-Driven Advanced Solid Tumors

The investigational drug to be studied in this protocol, BCA101, is a first-in-class compound that targets both EGFR with TGFβ. Based on preclinical data, this bifunctional antibody may exert synergistic activity in patients with EGFR-driven tumors.

NCT04429542
Conditions
  1. TNBC - Triple-Negative Breast Cancer
  2. Head and Neck Squamous Cell Carcinoma
  3. Squamous Cell Carcinoma of Anal Canal
  4. Uveal Melanoma
  5. Glioblastoma
  6. Colorectal Cancer
  7. Chordoma
  8. Squamous Cell Carcinoma of the Lung
  9. KRAS G12D
  10. KRAS G13D
  11. EGFR Amplification
  12. Epithelial Ovarian Cancer
  13. Hepatocellular Carcinoma
  14. Anaplastic Thyroid Cancer
  15. Pancreas Cancer
Interventions
  1. Drug: BCA101
  2. Drug: Pembrolizumab
MeSH:Carcinoma Carcinoma, Squamous Cell Glioblastoma Triple Negative Breast Neoplasms Squamous Cell Carcinoma of Head and Neck Carcinoma, Ovarian Epithelial Pancreatic Neoplasms Chordoma Thyroid Carcinoma, Anaplastic Lung Neoplasms
HPO:Anaplastic thyroid carcinoma Carcinoma Chordoma Glioblastoma multiforme Neoplasm of the lung Neoplasm of the pancreas Squamous cell carcinoma

i Single agent BCA101 - patients with the following tumor types will be eligible: 1) Squamous Cell Lung Cancer (SqCLC) 2) Squamous Cell Carcinoma of the Head and Neck (HNSCC) 3) RAS wild-type microsatellite stable Colorectal Carcinoma (RAS WT MSS CRC) 4) Triple Negative Breast Cancer (TNBC) 5) Chordoma 6) Squamous Cell Carcinoma of the Anal Canal (SCCAC) 7) Uveal Melanoma 8) Glioblastoma (GBM) 9) Gastric Cancer 10) Any solid tumor with a KRAS G12D or G13D mutation 11) Any solid tumor with EGFR amplification 12) Epithelial Ovarian Cancer 13) Hepatocellular Carcinoma (HCC) 14) Anaplastic Thyroid Cancer (ATC) 15) Pancreatic Cancer 16) Other EGFR-driven advanced solid tumors (if there is compelling data or evidence to enroll a patient with a tumor type other than those listed in 1 - 15, the treating physician may discuss the patient with the Sponsor to determine eligibility). --- G12D ---

i Single agent BCA101 - patients with the following tumor types will be eligible: 1. PD-L1 negative, EGFR-amplified SqCLC 2. RAS WT MSS CRC 3. EGFR-amplified TNBC 4. Any solid tumor with a KRAS G12D or G13D mutation ii. --- G12D ---

TNBC - Triple-Negative Breast Cancer Head and Neck Squamous Cell Carcinoma Squamous Cell Carcinoma of Anal Canal Uveal Melanoma Glioblastoma Colorectal Cancer Chordoma Squamous Cell Carcinoma of the Lung KRAS G12D KRAS G13D EGFR Amplification Epithelial Ovarian Cancer Hepatocellular Carcinoma Anaplastic Thyroid Cancer Pancreas Cancer Carcinoma Carcinoma, Squamous Cell Glioblastoma Triple Negative Breast Neoplasms Squamous Cell Carcinoma of Head and Neck Carcinoma, Ovarian Epithelial Pancreatic Neoplasms Chordoma Thyroid Carcinoma, Anaplastic Lung Neoplasms This is a Phase 1/1b, open-label study, which consists of dose escalation parts (Part A) followed by expansion cohorts (Part B) for both single agent BCA101 and combination BCA101 plus pembrolizumab. --- G12D ---

Planned expansion cohorts for single agent BCA101 include 1) PD-L1 negative, EGFR-amplified Squamous Cell Lung Cancer (SqCLC); 2) RAS wild-type, microsatellite stable Colorectal Carcinoma (RAS wt, MSS CRC); 3) EGFR-amplified Triple Negative Breast Cancer; and 4) any solid tumor with either a KRAS G12D or G13D mutation. --- G12D ---

Primary Outcomes

Description: Incidence and severity of AEs and SAEs

Measure: Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs

Time: 24 months

Description: Incidence and severity of AEs and SAEs

Measure: Tolerability of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs

Time: 24 months

Description: Incidence of DLTs during the first cycle of treatment with BCA101 monotherapy or the combination of BCA101 and pembrolizumab.

Measure: Incidence of Dose Limiting Toxicities (DLTs)

Time: 21 days

Secondary Outcomes

Description: Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST

Measure: Objective Response Rate

Time: 24 months

Description: Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST

Measure: Clinical Benefit Rate

Time: 24 months

Description: Determine PFS in each part of the study, per RECIST v1.1 and iRECIST

Measure: Progression free survival

Time: 24 months

Description: Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST

Measure: Duration of Response

Time: 24 months

Description: Determine survival rates in each part of the study.

Measure: Overall Survival

Time: 24 months

Description: AUC

Measure: AUC of BCA101 and pembrolizumab

Time: 24 months

Description: Cmax

Measure: Cmax of BCA101 and pembrolizumab

Time: 24 months

Description: Tmax

Measure: Tmax of BCA101 and pembrolizumab

Time: 24 months

Description: Ctrough

Measure: Concentration vs time profile of BCA101 and pembrolizumab

Time: 24 months

Description: Half-life

Measure: Half-life of BCA101 and pembrolizumab

Time: 24 months

Description: Incidence and titer of anti-drug-antibodies

Measure: Immunogenicity of BCA101 and pembrolizumab

Time: 24 months

12 A Phase 1 Study of TAS0612 in Patients With Locally Advanced or Metastatic Solid Tumors

The purpose of this study is to see if TAS0612 is safe in participants with advanced or metastatic solid tumor cancer.

NCT04586270
Conditions
  1. Advanced or Metastatic Solid Tumors
Interventions
  1. Drug: TAS0612
MeSH:Neoplasms
HPO:Neoplasm

The levels/changes of the phospho-proteins will be assessed and reported for target modulation.. Inclusion Criteria: - Dose Escalation: have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor) - Dose Expansion: have evidence of a solid tumor as outlined below that is locally advanced and/or metastatic (excluding primary brain tumor) - Cohort A: Human epidermal growth factor negative (HER2 negative) Breast Cancer with an NF1 mutation - Cohort B: Hormone receptor positive (HR+)/HER2 negative breast cancer after progression on endocrine therapy and a CDK4/6 inhibitor - Cohort C: PTEN loss or mutations - Cohort D: KRAS G12C mutation - Cohort E: KRAS G12D mutation - Have adequate organ function - Amenable to biopsy - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: - Participating in medical research not compatible with this study - Have not discontinued or recovered from previous treatments for cancer - Have a significant cardiac condition - Have untreated brain metastases - Have a primary brain tumor - Have a serious concomitant disorder - Unable to swallow or digest pills - Poorly controlled diabetes - Concomitant medications or substances that are strong inhibitors/inducers of CYP3A.Study Inclusion Criteria: - Dose Escalation: have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor) - Dose Expansion: have evidence of a solid tumor as outlined below that is locally advanced and/or metastatic (excluding primary brain tumor) - Cohort A: Human epidermal growth factor negative (HER2 negative) Breast Cancer with an NF1 mutation - Cohort B: Hormone receptor positive (HR+)/HER2 negative breast cancer after progression on endocrine therapy and a CDK4/6 inhibitor - Cohort C: PTEN loss or mutations - Cohort D: KRAS G12C mutation - Cohort E: KRAS G12D mutation - Have adequate organ function - Amenable to biopsy - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: - Participating in medical research not compatible with this study - Have not discontinued or recovered from previous treatments for cancer - Have a significant cardiac condition - Have untreated brain metastases - Have a primary brain tumor - Have a serious concomitant disorder - Unable to swallow or digest pills - Poorly controlled diabetes - Concomitant medications or substances that are strong inhibitors/inducers of CYP3A.Study Advanced or Metastatic Solid Tumors Neoplasms null --- G12C --- --- G12D ---

The levels/changes of the phospho-proteins will be assessed and reported for target modulation.. Inclusion Criteria: - Dose Escalation: have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor) - Dose Expansion: have evidence of a solid tumor as outlined below that is locally advanced and/or metastatic (excluding primary brain tumor) - Cohort A: Human epidermal growth factor negative (HER2 negative) Breast Cancer with an NF1 mutation - Cohort B: Hormone receptor positive (HR+)/HER2 negative breast cancer after progression on endocrine therapy and a CDK4/6 inhibitor - Cohort C: PTEN loss or mutations - Cohort D: KRAS G12C mutation - Cohort E: KRAS G12D mutation - Have adequate organ function - Amenable to biopsy - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: - Participating in medical research not compatible with this study - Have not discontinued or recovered from previous treatments for cancer - Have a significant cardiac condition - Have untreated brain metastases - Have a primary brain tumor - Have a serious concomitant disorder - Unable to swallow or digest pills - Poorly controlled diabetes - Concomitant medications or substances that are strong inhibitors/inducers of CYP3A.Study Inclusion Criteria: - Dose Escalation: have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor) - Dose Expansion: have evidence of a solid tumor as outlined below that is locally advanced and/or metastatic (excluding primary brain tumor) - Cohort A: Human epidermal growth factor negative (HER2 negative) Breast Cancer with an NF1 mutation - Cohort B: Hormone receptor positive (HR+)/HER2 negative breast cancer after progression on endocrine therapy and a CDK4/6 inhibitor - Cohort C: PTEN loss or mutations - Cohort D: KRAS G12C mutation - Cohort E: KRAS G12D mutation - Have adequate organ function - Amenable to biopsy - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: - Participating in medical research not compatible with this study - Have not discontinued or recovered from previous treatments for cancer - Have a significant cardiac condition - Have untreated brain metastases - Have a primary brain tumor - Have a serious concomitant disorder - Unable to swallow or digest pills - Poorly controlled diabetes - Concomitant medications or substances that are strong inhibitors/inducers of CYP3A.Study Advanced or Metastatic Solid Tumors Neoplasms null --- G12C --- --- G12D --- --- G12C --- --- G12D ---

Primary Outcomes

Description: Number of participants with DLTs during cycle 1

Measure: Dose Limiting Toxicities (DLTs)

Time: Baseline through Cycle 1 (28 day cycle)

Description: Percentage of participants with partial response (PR) or complete response (CR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Measure: Objective Response Rate

Time: Baseline through measured progressive disease (estimated up to 24 months)

Secondary Outcomes

Description: DCR: Percentage of participants who exhibit stable disease (SD), PR or CR.

Measure: Disease Control Rate (DCR)

Time: Baseline through progressive disease (estimated up to 24 months)

Description: DOR: Date of PR or CR to date of objective progression or death due to any cause.

Measure: Duration of Response (DOR)

Time: Estimated up to 22 months

Description: Baseline to objective progression or death due to any cause.

Measure: Progression Free Survival (PFS)

Time: Estimated up to 24 months

Description: Cmax of TAS0612

Measure: Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of TAS0612

Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle)

Description: Plasma concentration of TAS0612

Measure: Pharmacokinetics (PK): plasma concentration of TAS0612

Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle)

Description: AUC of TAS0612

Measure: PK: Area under the plasma concentration curve (AUC)

Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle)

Description: Tmax of TAS0612

Measure: PK: Time it takes to reach Cmax (Tmax) of TAS0612

Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle)

Description: t1/2 of TAS0612

Measure: PK: Time it takes for plasma concentration to fall by half its original value (t1/2) of TAS0612

Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle)

Description: All adverse events (AEs) per CTCAE v5.0

Measure: Safety and Tolerability

Time: Estimated up to 24 months

Description: Total proteins and phospho-proteins will be measured in blood samples collected at different time points. The levels/changes (dose- and concentration-dependent) of phospho-proteins will be assessed and reported for biochemical effects of TAS0612.

Measure: Pharmacodynamic: biochemical effects of TAS0612

Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle)

Description: Selected phospho-proteins will be analyzed in tumor tissue at baseline and on-treatment in dose escalation. The levels/changes of the phospho-proteins will be assessed and reported for target modulation.

Measure: Pharmacodynamic: molecular effects in tumor tissue of TAS0612

Time: Baseline through Day 1 Cycle 2 (28-day cycle)


HPO Nodes


HP:0002664: Neoplasm
Genes 1537
H19 RPS19 WT1 GPR101 CHEK2 MYD88 VEGFC PGM3 CTNNB1 PDGFRA IRF1 RHBDF2 PICALM FANCC GDNF RET PRKAR1A NELFA BCL10 KRT10 BLK TINF2 SMARCD2 NSD2 BRCA1 KRAS TRIP13 KCNH1 PERP CDH23 IKBKG MCC JAK2 MET GTF2E2 FOXC2 NF1 RAD51 TP53 ERCC4 WNT10A ASXL1 CTLA4 FLT4 DVL3 BRCA1 MLH3 NSD1 ERCC2 TSC2 FANCL RPS14 CDC73 TNFRSF4 STAG3 MSTO1 AIP EVC RET PLCD1 SDHB NEK1 POLH ASXL1 BRAF IL7 MAP2K1 ARSA BRAF COL4A5 CYLD KRT14 MLLT10 RASGRP1 H19 XIAP NTHL1 FGFR2 IGH DNAJC21 LETM1 MCM4 MYF6 CD70 FAM149B1 FGFR3 TERF2IP TNFRSF13C GLI3 DDX41 RPL26 PRLR SBDS LIG4 MGMT RERE KLLN FANCM WT1 PHB AXIN2 KIT PTEN TGFBR2 GJA1 PDGFRL STAT6 TYR CPLANE1 IFNG SIX6 JAG1 PALB2 SSX1 FANCG KIT MYO1H ELANE RPS19 H19-ICR KRT6B IDH2 PLCB4 FGFR1 BAP1 MINPP1 MST1 SMARCB1 PDGFRB RB1 FAT4 NF1 HFE SDHD WT1 TET2 BMPR1A RAF1 POLR1D CBFB SKIV2L IRF1 COL18A1 HMBS RET MMEL1 IGF2R JAK2 SEC23A BUB1B XPC ING1 AXIN2 KIT PALB2 MAGT1 STAC3 ALK SLC25A13 TMEM231 SHOX TDGF1 REST SMO SMARCA4 DNM2 TSR2 LIN28B GNAS WT1 CDKN1A DNAJC21 DKC1 BAP1 SRGAP1 ALX1 PTPN11 CBL APC SCN11A MAP3K1 RPL10 KLF6 PAX7 APC C1S NRTN BUB3 KRT5 LIG4 CARD14 GNAS MLH1 CDKN2A GNA11 TMEM127 ESR1 IL2RG KRT1 MET NF2 SDHAF2 SDHD WT1 MAP3K8 STAT1 PHOX2B PTPRJ PTCH2 CHD7 TERT LMNA ERCC6 EDNRB XPA PDGFRA OFD1 VHL SAMD9L SF3B1 FERMT1 BRCA1 GDF2 CASP8 TP53 LAMC2 GFI1B FANCD2 PYGL CR2 AR REST APPL1 APC CYP2A6 SEMA3C WT1 CDKN2A CTSA LRRC8A PHOX2B SMARCB1 NAGS FLI1 SOX2 RAD21 TMEM127 APC FGF3 BAP1 BUB1 RAD51 DKC1 RAD54B VHL EPCAM ASXL1 SRC HRAS BMP2 SLC25A11 PTH1R KRAS MYD88 NPM1 PTEN SH3GL1 PHOX2B TP53 SMAD4 XPA GATA4 MLH1 PMS2 STK11 FANCC DHCR7 PTCH1 CDC73 CYLD MEN1 CLCNKB CHEK2 RNF139 HABP2 POLE H19-ICR MMP1 RPL27 CC2D2A PIK3CA GPC3 ABL1 PALLD WASHC5 INTU ERCC5 DYNC2LI1 SLC22A18 TP53 CDH1 SHH MPL AKT1 NFKB2 NRAS PIGL CASP8 MYC KCNE3 DLST TAF15 TNFRSF13B GDNF EYA1 APC2 TNFRSF1B TCTN3 PPOX PNP PKHD1 BLM ODC1 IL12A TERT STK11 KRT17 IDH1 CIB1 RPL18 DVL1 ARHGAP26 PHOX2B CASP8 RPGRIP1L KRT6A SDHB FGFR2 VAMP7 JAK2 SRY DNMT3A EPAS1 KCNQ1OT1 MSH6 KRAS SDHB WNT5A DNMT3A RUNX1 TRIM28 DHCR24 USB1 VANGL2 GCM2 LIG4 KRAS SDHB ENG SEMA3D TRNS2 MINPP1 CASP10 NTHL1 LMOD1 SUFU FOXH1 CD81 ALX4 F13B BMPR1B RB1 CACNA1S CHIC2 VHL HRAS KIF11 KCNJ11 WRN SLC37A4 GNAQ LZTR1 CCND1 CPLX1 NR4A3 RYR1 NBEAL2 GATA2 TP63 APC KRAS HNF1B SUFU GNB1 MSX2 GPC3 CEL TCTN3 OCA2 MDM4 RB1 TMC6 ASCL1 AR BRIP1 CHEK2 AAGAB TSC1 TXNRD2 POLD1 CARMIL2 APC PIK3CA AKT1 POLE FAN1 RAD21 G6PC BRD4 PTCH2 MSH2 DHH EWSR1 SPRTN SDHC PTCH1 ALX3 CD79A TMEM67 INPP5E CCBE1 KRT6B BRCA2 ITK GINS1 HLA-DRB1 SNAI2 NBN PHOX2B BRAF CDH1 FANCE TYR GPC4 NF1 CD19 MVD AIP AR NBN TMEM107 BRIP1 ATRX BCHE MITF WRN BCR BCR NF2 SERPINA1 SDHB RABL3 PARN ANTXR2 TERT DPM1 IFIH1 GDF5 ZAP70 MEN1 TP53 GNAS BRCA2 TMC8 NODAL LETM1 VANGL1 TBXT BRCA1 FIBP FLT4 IL1B CCL2 FGFR3 SUFU MTAP ELANE CD19 HNF4A SAMD9 BUB1B KLHDC8B SLC26A2 FGFR3 FOXP1 PUF60 RUNX1 PTCH2 TRNK FLT4 TYROBP MPL KRAS RAD54L PIK3CA FAH CHEK2 CPLANE1 FAM20C CXCR4 DDR2 POU6F2 TMC6 SEC23B RET TRNP TFE3 TP53 NAB2 ANTXR1 MYSM1 SDHAF2 BTK TNFRSF10B DCLRE1C L2HGDH CDKN2A CYP11B2 BRCA2 SDHD TET2 TMEM216 BRAF PTCH2 TCF3 RPL11 NNT FLT3 BAX HAX1 IGF2 AKT1 FGFR3 MLH3 PLA2G2A TCF4 MLH3 NOTCH1 ERCC4 RRAS2 GPC4 DICER1 LZTS1 DOCK8 CASP10 GREM1 HPGD COL1A1 DCLRE1C IDH1 XRCC3 SUFU DNAJC21 PDGFRB TP53 NLRP1 WWOX TSC1 CTSC USP9X PDCD10 MEN1 ASCL1 RNF43 TNFRSF13C ESCO2 ZFPM2 AP2S1 PRCC HMBS ADA2 GANAB WT1 RNF43 HRAS KRAS SETD2 ATP6V1B2 FLT3 TJP2 BMPR1A PDGFB KIAA0753 PTEN STK4 NFKB1 BAP1 PMS1 MSR1 SLC26A2 RECQL4 MSH2 JAK2 ATRX FH RECQL4 FCN3 CD28 ASPSCR1 ADAR WHCR NOTCH3 GATA2 SMARCE1 CDKN2A RET ESCO2 EXT1 ERCC5 TET2 MBTPS2 NF1 OFD1 AGGF1 MVK KIT MUTYH HRAS KRIT1 FGFR1 TRIM28 CHEK2 CD79B GNAS BRCA2 KDSR BAX HACE1 MAP2K2 EDN3 ERCC2 CTNNB1 IL6 IGH PIK3CA MSH3 FZD2 SMPD1 SNAI2 PHOX2B SLC26A2 OFD1 PAX4 RB1 TRIP13 EWSR1 SCN9A PIK3R1 GBA EP300 PIK3CA HMMR KIT PDE6D ZSWIM6 SH3KBP1 SRP54 FUZ USP8 WT1 TERT MAFA FOXO1 GJB3 RAD51D POT1 SDHC PRKAR1A CREB1 SH2D1A WIPF1 WWOX PIK3CA NF2 HNF4A FAS RNASEH2A CD27 ATRX SPRED1 RPS14 FDPS RNR1 PALB2 NF1 MN1 TET2 GPC4 KDR SOX9 RAD51 MAX MYLK EP300 SHOX FOXE1 TCOF1 ESCO2 MYH11 HSPA9 MAD2L2 KRT9 CYP2D6 RFWD3 FANCE KRAS CCND1 LMO1 PTCH1 PORCN EDN3 PDGFRA DICER1 FANCA TERC CTBP1 SDHD ANTXR1 CXCR4 RAD50 BRCA2 MC1R MPL SLC22A18 MMP1 KRT16 F13A1 TSC2 ENG SETBP1 WT1 TET2 SDHC SMAD4 ZFHX3 GFI1 RNF113A STK11 KARS1 FOXE1 CDKN2B WT1 ERBB3 SMARCAD1 PDGFRL DMPK GTF2H5 NF2 CEBPA RPS28 PMS1 AKT1 PRDM16 NBN GCK SPINK1 ERBB2 JAK2 KIT DKC1 EXT1 JAK2 COL7A1 AXIN1 SLC22A18 NRAS ECM1 GNPTAB ABCA5 CDH1 NRAS ERCC6 VANGL1 RAD51C MYCN HBB TP53 SRY FANCI AKT1 MITF LEMD3 TARS1 TET2 NSD2 DAXX DYNC2LI1 OGG1 EXT1 TNFSF15 TERT ERCC6 DMRT3 SLC25A11 CTNNB1 VHL KLLN MLH3 EIF2AK4 GJB6 BARD1 OCRL GPR35 MYC DLST KRAS MSH3 RMRP PRKCD KLF6 NEUROD1 FANCG SLC17A9 BMPER FLCN SDHC SF3B1 STS GNA14 TERC MNX1 CAT TCF4 TUBB TRNQ BRCA2 IL12RB1 PDX1 CDKN2A SLC26A4 SDHC PPM1D NRAS PRKAR1A NRAS TAL1 KIF1B DNMT3A PDGFB MRAP ERCC3 CDC73 PRF1 RFWD3 PMVK RPL15 FGFR1 TP53 BICC1 HNF1A GATA1 RTEL1 RPS15A ERCC4 WRAP53 NR0B1 BCR FGFR2 SEC23A KRT17 NR5A1 VHL BLM BRAF ICOS POLD1 RPS27 FASLG CYSLTR2 PTEN PRKN THPO KIF7 NRAS TAL2 BRAF WDPCP DCC MSH6 NOP10 WNT10A PSAP ERCC2 CALR ACD SLX4 ACAN HABP2 GJB4 TET2 PHF21A ERCC3 MDH2 APC PALB2 RPL10 KRT17 PGM3 IL7R ARL6IP6 APC TCIRG1 NF1 SMAD4 PTPN3 PIK3CA ABCA5 FGFR2 TGFBR2 BRCA2 HNF1A RNASEH2C PAX6 IGH TTC37 DICER1 SRY GPC6 TOP2A KIT OFD1 PALB2 NRAS MC1R SDHD TFAP2A FGFR3 TNFRSF1B REST PTEN MST1R SCN4A BRCA2 CDKN2A FGFR2 ZIC2 EFL1 ECE1 NUP214 DDB2 GPC3 KCNQ1 PTEN HNF1B FN1 ASCC1 SPIB SRP72 PTEN FANCB KCNJ10 AKT1 KRAS KEAP1 INS DISP1 PTEN SASH1 CDKN1C ACTB TNFRSF13B MYH8 EDN1 IVNS1ABP NSUN2 TSC1 RAD51C MSH3 ATP7B RET PTPN12 STIM1 DHCR7 KRAS SFTPC BMPR1A XPC TMC8 KCNJ10 KDM6B STK11 KRAS GNAQ KRAS HFE HOXD13 B3GALT6 RPL5 KAT6B GATA2 MUC5B PIK3CA USP8 GDNF SMAD4 MVK RHBDF2 SSX2 CEP57 RAD51C NEK9 JAK2 PDGFB NRAS KRT1 PIK3CA MFN2 DOCK8 PTEN IL7 SDHC ATM AKT1 BRCA1 RELA GCDH PIK3CA IDH2 HRAS CTLA4 GPR143 ERCC2 GATA2 PTPN11 IGF2 SMAD4 NDUFAF6 CDH23 RPS7 RAD54B TP53 MUTYH GLI3 PTPN11 BRIP1 CDKN1B SF3B1 PTCH1 CIB1 ERCC3 PTPN11 TRPV3 GDNF IGLL1 PRKCD CTNNB1 PIK3CA PTPN11 SLCO2A1 FAH BRCA1 ETV6 BRCA2 EPCAM TP53 EXT1 BCL10 TRPS1 BMPR1A ATM MPL KRT17 MAX SLC12A3 ADA TERT UBE2T TSC2 TCTN3 MSH2 BDNF BTK SKI RPS20 NRAS RUNX1 DCC MSH2 RPS24 WT1 TRNF TFAP2A RPL35 RPS17 SDHA RARA CDC73 SBDS POLH BRAF LAMB3 RNF6 PIEZO2 KCNQ1OT1 CCM2 PHKA2 POU2AF1 TP53 TREM2 ABCC8 EXT2 ALK PHKG2 NUTM1 SLC26A4 PTCH1 MUTYH PALLD NBN FANCA SQSTM1 ELMO2 ACP5 TWIST1 TRIM37 RPL31 HFE RET DLC1 SDHB EP300 TREX1 HSPG2 ATP7A MSH6 C2CD3 CHRNG SRP54 TINF2 BUB1 PSENEN SMAD4 NF1 ERCC3 ARID1B RMRP WAS GATA2 MAPK1 BIN1 COL7A1 EDN3 PIK3CA IGF2 H19-ICR TUBB FH MLH1 TNFSF12 PIK3R1 RASA1 F5 SH2B3 CTNNB1 FOXI1 SUFU TLR2 SRSF2 CDKN1B GJC2 OPCML LEMD3 FIBP TRNS1 HNF1A VHL PTEN PRKAR1A MSH2 CYLD CTHRC1 COL7A1 DDB2 SDHC GJB2 LIG4 MDM2 LAMA3 CHEK2 MTOR CDON SMARCE1 TAF1 GNAQ TP53 RAD54L WWOX BMPR1A CCND1 GFI1 BCL10 PTEN CTNNB1 DHX37 SLX4 FGF8 XRCC4 TRIP13 CDC73 BIRC3 NOTCH3 DIS3L2 PKD2 KIF1B GNA11 ARMC5 CREBBP DIS3L2 HRAS LMX1B BAP1 BRCA2 POT1 ABCB11 AURKA RASA1 SMARCB1 ALX4 GPC3 MGAT2 PAX3 IGHM LMNA TCF4 GATA1 TRNK IDH1 LRP5 CALR FH RET SEC23B APC TET2 SETBP1 WT1 PMS2 POLR1C SIX3 EPHB2 RPL35A RET TINF2 CD28 CYP26C1 MNX1 ALX3 KIT CPOX GJB2 DLL1 MSTO1 RSPO1 TEK EXT2 ABCC6 COL2A1 GNAS FH FASLG BAP1 COL14A1 YY1 RAG2 RB1CC1 MAP2K1 RHOH STAR CREBBP RECQL4 EVC2 HBB ERBB2 ABL1 NDP SUFU NF2 MSH6 ATP7A TSC1 FAS SLC6A17 MS4A1 NQO2 FLCN EXTL3 SOS1 RNASEL NPM1 KIT GNAI3 TRNH RAG1 HRAS BUB1B IGF2 PLAG1 FANCD2 BCL2 NEK1 KIT ATP7A PIK3CA SMARCB1 PCGF2 LIG4 BCL6 NUP214 FLNA IRF5 ACVR1 GAS1 DYNC2H1 RSPRY1 TRAF7 RNASEH2B REST RPS29 TGIF1 TERT PIGA TP53 CDK4 GPR101 ACVRL1 SAMHD1 MSL3 MAPRE2 SLC45A2 CTNNB1 ADA KLF11 NKX2-1 GLI2 PKD1 MAP3K1 SRP54 TNFSF12 ND5 CRKL RASGRP1 BCL10 RPS26 GLI3 TRNL1 AR SDHA RB1 MLH1 MC2R TGFBR1 KIT CYP11B1 AXIN2 EGFR PIK3CA RECQL4 EXOC6B SMO SFTPA2 NRAS CDKN1B TP53 PIK3CA MSH6 ACTG2 POT1 SDHB RNF6 CALR KCNN3 C11ORF95 TSC2 CD96 SOS1 COL2A1 SMAD7 GLI1 FANCF MPL CDH1 BRCA2 BRAF ATR SDHA FLCN DICER1 IL1RN ICOS AIP RSPO1 DICER1 GCM2 XRCC2 DNASE1L3 PPP2R1B TGFBR2 MTM1 CDKN2C SIX1 MEN1 POU6F2 SRD5A3 STAT3 ERCC3 TG ASXL1 CDKN2B CYLD NHP2 CCDC22 TBC1D24 BLNK DIS3L2 SH2B3 MPLKIP AHCY PCNA EXT2 EXT2 MEN1 PARN WRAP53 TP53 HBB GABRD NUMA1 APC ZSWIM6 BRCA1 GJB2 KCNAB2 AIP USF3 RUNX1 H19 HDAC4 SDHD UROD PDGFRB CR2 HRAS CDH1 ERBB2 TNPO3 LPP SDHD IL2RG ATM BARD1 TREX1 POLE C2CD3 ERCC4 SLC25A13 PNP KRAS SRSF2 SDHB FGFR3 CASR CASP10 TET2 CTC1 ENPP1 SOX6 PIK3CA BMPR1A ERCC2 TERC CBL ADAMTS3 PIGL BCR SAMD9L NOD2 CBL TGFBR2 MALT1 SEMA4A ANTXR2 SLC37A4 TBX2 DHH STS SDHB TERT KRT16 DZIP1L RTEL1 SDHD CCND1 AKT1 FOXI1 CDK4 NSD1 MLH1 FLCN DLEC1 FGFRL1 MTMR14 GCGR TBX18 CREBBP MXI1 APC BCL10 COL11A2 TERT MC1R SCN10A RPS10 SMO BRCA2 KIT ATM PRKN MRE11 KIF1B KCNH1 VHL GPR101 GNAS PMS2 ACD WDPCP MAD1L1
HP:0007378: Neoplasm of the gastrointestinal tract
Genes 380
MLH1 STK11 RPS19 KIT MLH1 AXIN2 CD81 AXIN1 HFE PRKAR1A WWOX MSH2 CTHRC1 CDKN1B MEN1 RAD51C RPL5 IRF1 RHBDF2 SDHD RNF43 TP53 WT1 HBB STAT1 SDHC HMBS ADA2 MDM2 MTOR SDHB MITF KCNJ11 RNF6 SMAD4 RNF43 SLC37A4 PTPRJ KRAS DAXX RHBDF2 LMNA C11ORF95 BMPR1A TJP2 CEP57 TNFSF15 BMPR1A NFKB1 BLK PMS1 PTEN EDNRB APC MSR1 KRAS SMAD7 CTNNB1 PDGFRA MSH2 CTNNB1 SUFU TRIP13 JAK2 ATRX TRIP13 GDF2 MLH3 CASP8 CEL MCC DIS3L2 BARD1 TP53 GPR35 MET RELA PYGL TP53 APPL1 CHEK2 IL1RN AAGAB APC ICOS MSH3 CDKN2A BRCA2 PRKCD BRCA1 POLD1 APC SEMA3C POT1 ABCB11 SMAD4 NEUROD1 MLH3 RPS7 CDKN2C FLCN SDHC AURKA FAN1 CDKN2A RAD21 G6PC POU6F2 MUTYH MSH2 TCF4 SPRTN MUTYH SDHC PTCH1 IL12RB1 TRIM28 CDKN2B CHEK2 TMEM67 GDNF PDX1 GATA1 SDHC INPP5E PRKCD BAX ARSA APC EDN3 BUB1 RASGRP1 FAH RAD51 SEC23B APC RAD54B SETBP1 AHCY BRCA2 PMS2 EPCAM MSH3 RPL15 EPCAM SRC HNF1A SMPD1 RPL35A BMP2 RET MEN1 RPS15A PAX4 GPC4 TP53 PTEN TERF2IP BMPR1A TNFRSF13C KIT HBB TP53 NBN SMAD4 RPL26 PIK3CA APC CPOX MGMT BLM MLH1 POLD1 RPS27 KLLN BRIP1 FASLG AXIN2 USF3 PTEN H19 UROD TGFBR2 WRN SH3KBP1 CR2 CDH1 SERPINA1 TNPO3 MEN1 SDHD PDGFRL STAT6 POLE COL14A1 RPL27 CC2D2A MSH6 TREX1 POLE SLC25A13 RAD51D PSAP GPC3 RPS20 JAG1 GNAS PALLD SDHB BRCA2 PALB2 ACD FGFR3 HABP2 DCC PIK3CA MSH2 RPS24 CASP10 HBB RPL35 RPS17 FAS ERBB2 APC TP53 BRCA1 PALB2 RPS19 H19-ICR PIK3CA IL1B FAS AKT1 BMPR1A PIEZO2 MS4A1 NFKB2 KCNQ1OT1 APC CD19 PHKA2 HNF4A EP300 SMAD4 POU2AF1 PTPN3 MST1 PIK3CA ABCC8 FOXE1 TGFBR2 KIT TNFRSF13B FGFR2 TGFBR2 HNF1A PHKG2 SEMA4A BUB1B HFE SLC37A4 SDHD MUTYH PTCH2 BMPR1A TTC37 SDHB TERT PPOX KRAS PKHD1 ODC1 IL12A PIK3CA SKIV2L DZIP1L NRAS FAH RPL31 HMBS CHEK2 HFE MMEL1 IGF2R RPL18 SDHD CCND1 PDGFRA DLC1 DICER1 IRF5 BUB1B SEC23B SDHB REST RPGRIP1L MLH1 PTEN MSH6 RAD50 NAB2 FLCN AXIN2 DLEC1 ECE1 SLC25A13 BUB1 GPC3 KCNQ1 SMAD4 CDKN2A ENG SETBP1 APC ASCC1 RPS29 SPIB SDHC PTEN MC1R MSH6 SDHB TSR2 RPS10 RPL11 AKT1 KEAP1 TRIM28 CDK4 INS ACVRL1 CDKN1A PIK3CA IGF2 H19-ICR STK11 CDKN1C IGF2 MRE11 CDKN2B FH BAP1 TNFSF12 WT1 APC F5 PLA2G2A PDGFRL KLF11 MLH3 DMPK GNAS PMS2 CTNNB1 ATP7B KLF6 TLR2 RPS28 PMS1 CDKN1B PTPN12 TNFSF12 AKT1 SDHB APC ENG NRTN BCL10 SEMA3D DOCK8 RPS26 GCK BMPR1A GREM1 SDHA MINPP1 CASP10 BUB3 NTHL1
Protein Mutations 5
C10D G12D G12V G34A V600E