SNPMiner Trials by Shray Alag

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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation G12D

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 12 clinical trials

Clinical Trials


1 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

2 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

3 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

4 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

5 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

6 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)

7 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

8 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

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 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

11 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

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 1522
SF3B1 GFI1B IGF2 FIBP RPS7 WT1 COL7A1 TREX1 HSPG2 CASP8 SLC22A18 MC1R TFE3 KRAS PLAG1 OFD1 BRAF NUMA1 KRT16 PSENEN CTPS1 APC SOX9 FANCM OPCML CDKN2A RPS15A CTNNB1 SDHD EDN3 FCN3 NELFA GJC2 MALT1 HPGD GLI1 CD70 SPINK1 LETM1 PMS1 LRP5 HNF1B EXT1 TCF4 ELMO2 MET ANTXR1 KRT16 KRT10 PAX4 SETBP1 TERT WT1 SMARCB1 GJB6 HRAS STK11 BUB1B GNPTAB MYD88 MCC GJB2 BRCA1 TP63 PDGFRL TARS1 NF1 FGFR3 KARS1 BARD1 BRIP1 GATA2 IL1RN BRAF CD81 TNFRSF13B TYROBP AR LIG4 KLF11 ABL1 MVK BMPR1A PIK3CA B3GALT6 SLC37A4 SOS1 TSC1 FGFR3 ATRX FANCG TET2 KIT SRP72 MPL TP53 SMAD4 EVC2 MAPRE2 DLST BRCA1 DICER1 HRAS AKT1 RNR1 TSC1 TNPO3 XRCC4 DNMT3A NEUROD1 THPO MN1 NOD2 SRSF2 PPM1D FLT4 ATP7A IL7 KRAS GDNF WNT10A EPAS1 COL1A1 IL1B MRAP ADAMTS3 PRKCD SUFU PTCH1 ERCC3 KRT14 CXCR4 HOXD13 IGF2 LIG4 PALB2 BLM NRAS ERCC3 FOXP1 SDHD TP53 PKD2 PDX1 TINF2 ADA2 MYF6 RHBDF2 POU6F2 PHKG2 CDKN2A RUNX1 ERCC2 MAP2K2 WT1 USB1 GATA4 FGFR2 ACD CR2 MUTYH ARL6IP6 FAH MSH2 RASA1 NEK1 SOX6 NR0B1 LIG4 CDKN2B NF1 NF1 POLE RPL35 SRY SDHAF2 FANCL CPLX1 FAS PRKAR1A PHB SDHA CALR PIK3R1 FAN1 TET2 TMEM216 RSPO1 SEMA3D MDM4 SDHD HRAS NUP214 GJA1 PIK3CA CCND1 RNF6 MSH2 C11ORF95 MVK MCM4 FLI1 TINF2 KIAA0753 ECM1 ARSA ERCC2 SOX2 SDHC SLC26A2 MPL VANGL1 PUF60 RAD51D POT1 CR2 ESCO2 FOXE1 PMVK SRY GJB4 TRIM37 KIT EXT2 PDGFB KIF1B FANCF IGF2R MLH1 GDNF PIK3CA ASCC1 ASCL1 TCIRG1 APPL1 RPS19 BCL10 IGF2 NRAS FLT3 STAT1 BCL10 RMRP GNAI3 KRAS GPR101 BAP1 NKX2-1 MAX BMPR1A DDB2 SMARCB1 RAD51 FGFR3 ALX4 BTK MSH6 NOTCH3 DICER1 CXCR4 CCBE1 RET WT1 TP53 PALLD RNASEH2B WT1 ATR CCND1 KCNQ1OT1 SMAD4 AHCY STK11 FANCC TRNK BCL6 SMAD4 SKIV2L HMBS TP53 TERT PHOX2B SNAI2 BRAF TCOF1 FANCI NRAS REST SDHC HBB HFE CREBBP MET SEC23A CEP57 CTLA4 TRIM28 SMAD7 GNAS BRCA2 PALB2 FGF8 SBDS RET ALK GJB2 CPLANE1 GPC3 TCTN3 PTEN RB1 INTU CYP26C1 LEMD3 PRLR CDON NLRP1 GPR101 DHH HNF4A MMEL1 DNASE1L3 RASGRP1 ATRX CHEK2 FANCA SPRED1 DNM2 FLT4 CHEK2 RPS19 KLLN HACE1 HNF1A PTPN11 CDKN1B GAS1 BRCA2 KCNQ1OT1 NPM1 FGFR3 MC1R MINPP1 PTPN11 TSC2 ABCA5 BRCA2 PLCB4 SCN11A HNF1A BRAF RB1 CBL ARHGAP26 SUFU PTPRJ C1S APC IRF5 GNAQ GDNF TERT MYSM1 XPC TMC8 COL4A5 ERBB3 SLC26A4 CD96 NSUN2 PDGFRA FERMT1 TYR DNAJC21 MSH2 SH3GL1 TUBB RET BRAF ESR1 PAX3 RHBDF2 RTL1 WRN DYNC2LI1 ELANE EXOC6B RPS26 EWSR1 VHL PIGA GCGR POU6F2 RNF43 POLE BRAF MNX1 SFTPA2 CDH23 ASCL1 APC ACVR1 PIGL BAX RAG2 RSPO1 MSH3 PGM3 FGF3 FANCE MPL TP53 COL7A1 BUB1 TET2 PALB2 ACTB PNP SDHC EDN3 XPA TMC6 NEK1 GNA11 KAT6B KRT1 RUNX1 PAX7 NOTCH1 ENG CTNNB1 ETV6 MPLKIP PARN CDKN2A PTPN3 STAG3 MDM2 TP53 LAMC2 NBEAL2 VAMP7 GNA14 DCLRE1C CBL GCDH FANCC AXIN2 PYGL SOS1 BLK WRAP53 IDH1 KRAS CCM2 APC ASXL1 ATP7B ERCC3 SF3B1 EP300 BRCA2 MGAT2 NRTN CDKN2A DICER1 PMS1 RPS10 TBC1D24 FAH BRCA2 ASXL1 BCR C2CD3 KRAS IDH1 IGLL1 RASA1 BRCA2 CHEK2 PTCH1 RNF113A BRAF MBTPS2 EDNRB IGHM PDGFRB RAF1 MEN1 FASLG TUBB NDUFAF6 FOXI1 TGFBR1 EPCAM CYLD SDHB APC CYP2D6 TAF1 KRT17 BRCA1 BUB1B BAP1 GDF2 BUB1B ERCC2 TP53 KRT5 GATA2 BRCA1 RAD54B MRE11 STAC3 DNMT3A MLH1 BCHE EDN3 CDKN1B AURKA NRAS FLCN IDH2 EDN1 ESCO2 USF3 IGH POT1 ACVRL1 JAK2 NBN NRAS SQSTM1 TMEM127 ZFPM2 SLC12A3 NTHL1 ADA CHIC2 STAT3 SETBP1 FANCB FIBP STAT3 STK11 MLLT10 SFTPC HDAC4 NUP214 GLI2 SLX4 TSC1 ERCC6 TP53 CLCNKB KLF6 OGG1 JAK2 PAX6 RECQL4 RPL31 MYO1H FH RPGRIP1L SLC45A2 RPL10 RPL10 HMBS GDF5 TNFRSF10B PIK3CA GABRD TP53 BRCA2 SEMA4A BCR PALB2 ASXL1 KRT6B CCDC22 SAMD9 DMPK DCC ERCC5 RPL5 CTNNB1 RPS27 TRNS2 PTCH1 PTEN TFAP2A RPS24 RPL35A RET AXIN1 HNF1B ARMC5 UBE2T SRP54 SSX2 DKC1 ERCC3 JAK2 GNA11 LAMB3 GJB2 NFKB1 KCNQ1 GLI3 PIK3CA KANSL1 CASP8 MYC RECQL4 ACAN CACNA1S BDNF KIF11 MDH2 MSL3 FGFR1 TERF2IP HFE NFKB2 TOP2A GFI1 SRD5A3 PHKA2 MAX POLE MAP2K1 EYA1 RNF43 ALX3 SETD2 ERCC4 CTLA4 SIX3 LEMD3 OCRL CDH23 DZIP1L MSH3 AR CDC73 PDGFRL TWIST1 POU2AF1 DKC1 CALR LIN28B KRT6A GATA1 MC1R DIS3L2 CD28 CDC73 ADA2 UROD CIB1 TSR2 WNT5A TET2 PHOX2B BMPER KIT DLC1 MSTO1 H19-ICR SLC25A13 ADAR TMEM67 BMPR1A MLH3 POLR1C KRT6B FH EFL1 TERC BUB3 FOXC2 NOTCH3 KIT NSD1 FGFR2 SLC6A17 MAP3K1 TRIP13 MEG3 RRAS2 BMPR1A NF1 DPM1 LIG4 PARN RHOH BRCA2 NF1 TAF15 RFWD3 VHL H19 BCR KRAS VANGL2 KRAS SDHD DVL3 BIN1 ABL1 GPC3 HAX1 FANCA GDNF NHP2 IGF2 VHL CCL2 EXTL3 RUNX1 PRKCD BLNK MSH6 SLC22A18 IL2RG PTH1R SDHB AIP WDPCP APC KCNJ10 ASPSCR1 OCA2 TP53 WT1 SPRTN TET2 TAL1 L2HGDH KIT SDHC ERCC4 GPR143 PRKN SMAD4 SEMA3C TRNS1 BRCA1 SHOX PCNA FANCG CREB1 TRNH VHL MYLK BAP1 SUFU ANTXR1 POLD1 NODAL IGH JAK2 MS4A1 MEN1 TSC2 GATA2 DHCR7 TINF2 F13B RB1 COL7A1 SCN4A BMPR1A DDB2 CDKN2A SDHD CYP11B2 IL7 ARID1B KIT FGFR1 RET CDKN2A LAMA3 CHEK2 TBX2 TBX18 HNF4A GPC4 SHH LMNA BMP2 YY1 AKT1 WT1 BAP1 FZD2 SH2B3 BTK GATA1 RAD54L ATM CTBP1 PTEN SRY RYR1 CTHRC1 MFN2 PTEN RAD21 PTEN MYC SLC26A2 TP53 CTNNB1 RAD51C NAB2 NLRP1 SUFU DLL1 PSAP SDHB REST TGFBR2 TRIP13 IGH ABCC8 IL6 CPLANE1 H19 FANCD2 FGFR2 RET PKD1 DNMT3A REST CHEK2 GNAQ MXI1 BRIP1 DYNC2LI1 GNAS TP53 GLI3 DIS3L2 NRAS PICALM WT1 BAP1 MEN1 TXNRD2 MGMT PTEN MYD88 GNAS POT1 AGGF1 BUB1 PTEN PORCN HFE NUTM1 PHOX2B MSX2 PMS2 SLX4 H19 USP9X RPL27 GNAS SEC23B CBL CD28 PKHD1 AXIN2 TRPV3 KLLN SSX1 TSC1 PPOX KRT17 CARD14 HRAS TCF3 RPL11 CC2D2A GREM1 CHEK2 AP2S1 NRAS TRNL1 ALX1 CREBBP TCTN3 TET2 ESCO2 DOCK8 NRAS STK11 GCM2 TTC37 WT1 SMAD4 DAXX MITF BCL2 DIS3L2 POLR1D TDGF1 KRAS TNFRSF13C KIT PHOX2B SF3B1 RPL15 NF1 TERT TNFRSF1B FANCD2 MLH3 IL7R GPC4 H19-ICR SLC17A9 MEN1 MST1R KIT RAD50 TJP2 DNAJC21 PDCD10 MUTYH IL12RB1 SH2D1A FGFR2 NBN KRAS KIT CASR ENPP1 SDHB HRAS IKBKG PNP EXT2 BRD4 SMARCB1 REST COL11A2 TG KIT LIG4 SUFU NBN RSPRY1 CYSLTR2 SDHD AAGAB BLM RAG1 RNF139 RB1CC1 ACD PTPN11 SLC26A2 TREX1 BMPR1B DDR2 ZAP70 MNX1 MAGT1 AIP GATA2 AR STAR IFIH1 IDH2 BRCA1 USP8 RB1 FGFRL1 SMO USP8 RMRP SLC25A11 MLH3 FUZ DOCK8 SUFU NF2 KDR KRAS RPS14 CASP10 SRP54 ZSWIM6 TBXT PTCH2 EWSR1 TNFRSF13C MTAP NQO2 RPL18 DNAJC21 GCK ERCC6 KDM6B EXT1 SBDS CCND1 SDHAF2 KCNH1 CYLD LMOD1 PDGFRA CAT CHRNG TRNQ ADA NRAS TLR2 SHOX FGFR3 BCL10 TYR KRAS COL2A1 PTCH2 SMO GBA MSTO1 TREM2 JAK2 TMEM231 MSH2 ASXL1 RET DHCR7 NBN PIK3CA NSD2 SDHB EIF2AK4 PALB2 KIF7 PTPN11 PIK3CA HLA-DRB1 STIM1 TMC6 KIF1B TNFSF15 RELA AKT1 NPM1 APC SDHA SDHB STAT6 CDKN1C CDC73 PTCH2 KANSL1 ZSWIM6 FLCN HBB LZTS1 FN1 TRAF7 ACP5 CTNNB1 MLH1 EXT2 RNASEL RNASEH2A IL2RG ATP7A CDK4 CYP11B1 MMP1 SDHB ATRX ACTG2 FOXH1 OFD1 NEK9 STS MUC5B PRKCD PTPN11 PTCH2 LRRC8A RPL26 MSH6 NNT LZTR1 CDC73 PTEN AKT1 AKT1 SASH1 HRAS ANAPC1 PTPN12 KCNJ11 TCF4 GATA2 MLH3 ERCC4 GNB1 DISP1 IDH1 BCR GANAB MSH6 NR5A1 TSC2 GFI1 TNFSF12 TRNP MAPK1 IFNG FLT4 MTM1 WWOX HABP2 RPS28 HRAS SLCO2A1 ND5 SDHB CHD7 BRIP1 SLC37A4 MC2R XRCC3 TNFRSF4 NAGS PHF21A ZIC2 PCGF2 SMARCE1 CTNNB1 SRP54 CDH1 CDK4 RPS20 KCNJ10 RAD21 RNF6 COL14A1 SMO CD19 WRN SRGAP1 CDKN2C AXIN2 GPC6 WWOX HSPA9 FOXI1 CPOX RPS17 APC2 MYH8 SERPINA1 ATM LMX1B ENG POLH TGFBR2 DHX37 VEGFC KIF1B KRT17 DDX41 SPIB CBFB HRAS BCL10 PIGL FGFR1 NSD1 F5 KCNN3 BAX PIEZO2 RECQL4 CREBBP KIT PDGFB PDE6D ABCA5 AKT1 KLHDC8B TNFSF12 EPCAM RARA MLH1 GINS1 EVC PIK3CA FANCE WIPF1 NF2 PDGFRA PRKAR1A CDH1 SDHD PRCC TRNF PTCH1 TNFRSF1B WNT10A WWOX MAD1L1 MTOR WDPCP RNASEH2C NSD2 SAMD9L FH LPP NF1 KRIT1 NTHL1 IL12A HNF1A CDH1 SMARCB1 SMARCE1 CD19 FH FDPS TRPS1 ERCC4 SMPD1 SMARCD2 BRCA1 MPL CRKL SEC23A EXT1 PERP ATM FOXE1 CDKN2B CTSC SIX1 FAM149B1 CDH1 RAD51C ALX3 DLST TRIP13 ING1 PDGFRB FLT3 COL18A1 MST1 TGIF1 TMEM107 SRSF2 TRIM28 BAP1 ANTXR2 CD79A PIK3R1 MAP3K1 NOP10 PIK3CA POLD1 KDSR CCND1 TP53 TMC8 ALK MAP2K1 CD79B SDHC ECE1 PALLD CTSA PRDM16 IVNS1ABP CALR FLNA GPR101 BRCA2 ERCC2 DYNC2H1 TFAP2A COL2A1 DVL1 TERT APC TERT TEK EXT2 TERC ALX4 OFD1 LMO1 PDGFRB RPS14 DCC RTEL1 INS TSC2 FAM20C MYH11 GPC3 SCN9A SMAD4 RASGRP1 HBB TGFBR2 RERE NDP PLA2G2A TCF4 MAD2L2 SKI AIP HMMR SDHC SNAI2 PIK3CA LMNA PGM3 ABCB11 TAL2 WT1 VHL PIK3CA TCTN3 SAMD9L ICOS GLI3 RB1 SLC25A13 SDHC DCLRE1C GCM2 VANGL1 SIX6 WT1 PMS2 KCNH1 BARD1 H19-ICR GNAS TERT CIB1 B3GALT6 GJB3 ERBB2 SDHA KRAS CDC73 TNFRSF13B TET2 FGFR3 WAS SEC23B TGFBR2 TP53 NF2 SMARCA4 NF2 SLC26A4 ANTXR2 WRAP53 FAS SAMHD1 TP53 TET2 ATP7A PTEN SH3KBP1 CARMIL2 MVD PDGFB ABCC6 G6PC1 TRNK KRAS GPC3 PTEN NF2 JAK2 DMRT3 GNAQ RAD51 GTF2H5 TMEM127 TERT RUNX1 FAT4 AR HABP2 NR4A3 EP300 MINPP1 OFD1 RASA1 DLEC1 BIRC3 AIP CD27 PHOX2B BMPR1A KCNE3 PLCD1 RAD51 KRT1 MSH3 MITF EPHB2 DHCR24 RABL3 KRT17 XRCC2 NRAS ITK VHL BICC1 RECQL4 SMARCAD1 MYCN RET CTC1 PTCH1 JAK2 SRC SDHB PHOX2B AKT1 KEAP1 JAG1 VHL LETM1 NLRP1 MEN1 BRCA2 FLCN C2CD3 RFWD3 XPA APC APC SDHD FOXO1 MAFA WHCR GPC4 MLH1 ICOS CDKN1B MTMR14 KIT DICER1 EP300 ZFHX3 MMP1 PRKAR1A KRT9 F13A1 CTNNB1 MPL INPP5E NF1 DKC1 TERT DLK1 SCN10A STS RPS29 PTEN FLCN LRBA ELANE GTF2E2 ATM PIK3CA GPR35 CYLD RAD51C CDKN1A WT1 DICER1 PIK3CA TERC PIK3CA SLC25A11 GNAS CEBPA ATP6V1B2 RET XPC EXT1 BRCA2 SH2B3 ERCC3 BRCA2 RTEL1 WASHC5 ERCC2 AKT1 KCNAB2 CYLD STK4 POLH ERCC5 CDH1 CEL XIAP MSR1 TP53 TET2 DHH PRKAR1A
HP:0007378: Neoplasm of the gastrointestinal tract
Genes 375
BRIP1 SLC37A4 RPS7 PDGFRA MSH2 POLD1 CTNNB1 TREX1 JAK2 MS4A1 CASP8 MEN1 RPS20 RAD21 RNF6 RHBDF2 RTL1 WRN COL14A1 BMPR1A CDKN2C RPS26 SDHD AXIN2 POU6F2 RNF43 APC KIT CPOX RPS17 CDKN2A SERPINA1 CDKN2A HNF4A RPS15A ENG APC TGFBR2 SDHD BMP2 BAX SPIB BCL10 MSH3 F5 PMS1 PIEZO2 TP53 BUB1 TCF4 CTHRC1 SDHC TNFSF12 PAX4 SETBP1 EPCAM PTEN EDN3 TP53 CTNNB1 MLH1 NAB2 STK11 SUFU BUB1B PSAP SDHB REST TGFBR2 ENG ABCC8 WWOX MCC H19 PTPN3 MTOR BRCA1 MDM2 PDGFRL NF1 AXIN2 PYGL BARD1 BLK TP53 IL12A CDH1 APC CD19 IL1RN FH ATP7B MEN1 CD81 SMPD1 NRTN MGMT CDKN2A KLF11 BMPR1A PIK3CA SLC37A4 PMS1 RPS10 CDKN2B FAH BUB1 PTEN BRCA2 HFE TRIP13 PMS2 RPL27 MST1 SEC23B PKHD1 AXIN2 AKT1 PTCH1 PPOX TNPO3 TRIM28 BAP1 EDNRB NEUROD1 MEN1 RPL11 CC2D2A FASLG GREM1 CHEK2 POLD1 CCND1 EPCAM APC ECE1 IL1B GDF2 BUB1B DOCK8 PRKCD TP53 STK11 RAD54B TTC37 MRE11 SMAD4 DAXX MLH1 BLM DIS3L2 KRAS SDHD AURKA PDX1 APC RPL15 FLCN ADA2 RHBDF2 PHKG2 INS MLH3 GPC4 H19-ICR SMAD4 USF3 ACD CR2 MUTYH KIT HBB FAH RAD50 ACVRL1 MSH2 TGFBR2 TJP2 PLA2G2A CDKN2B MUTYH IL12RB1 NTHL1 POLE RPL35 NBN SDHC FAS SETBP1 KIT PIK3CA LMNA ABCB11 WT1 SDHB FAN1 ICOS SEMA3D SLC25A13 SDHC PIK3CA AAGAB RPL31 PMS2 RPGRIP1L MSH2 C11ORF95 GNAS HMBS ARSA SDHC BRCA2 SEMA4A TNFRSF13B PALB2 BRCA1 RAD51D POT1 FGFR3 DMPK FOXE1 SEC23B DCC TP53 RPL5 RPS27 RPS24 RPL35A FAS IGF2R PTEN ASCC1 SH3KBP1 AXIN1 G6PC1 APPL1 KRAS RPS19 IGF2 KRAS CASP10 STAT1 PTEN TNFRSF13C NFKB1 KCNQ1 RPL18 GCK EP300 BMPR1A RAD51 MINPP1 TERF2IP MSH6 DLEC1 HFE PDGFRA NFKB2 PHKA2 BMPR1A PALLD POLE TLR2 RNF43 SMAD4 AHCY PTCH2 SMAD4 SKIV2L MSH3 MITF HMBS MSH2 DZIP1L PDGFRL POU2AF1 SDHB NRAS GATA1 HBB HFE PALB2 UROD PIK3CA MET TSR2 SRC SDHB DLC1 KEAP1 JAG1 TNFSF15 CEP57 RELA AKT1 H19-ICR APC SLC25A13 TRIM28 SDHA TMEM67 BMPR1A MLH3 STAT6 FLCN CDKN1C SMAD7 APC APC RET HBB MLH1 CDKN1B BUB3 GPC3 DICER1 MLH1 PRKAR1A TRIP13 CDK4 MEG3 BMPR1A CTNNB1 MMEL1 INPP5E ATRX RASGRP1 CHEK2 TERT DLK1 SDHD CHEK2 RPS19 RPS29 RPL26 KLLN GPC3 HNF1A CDKN1B GPR35 IGF2 PTEN KCNQ1OT1 RAD51C CDKN1A MC1R PRKCD WT1 MSH6 PTPN12 PIK3CA GNAS KCNJ11 HNF1A MLH3 SDHB APC BRCA2 MSH6 TP53 SPRTN PTPRJ TNFSF12 AKT1 SDHC APC IRF5 SMAD4 GDNF SEMA3C HABP2 RPS28 CEL MSR1 SDHB
Protein Mutations 5
C10D G12D G12V G34A V600E