There are 6 clinical trials
Background: A new cancer therapy involves taking white blood cells from a person, growing them in the lab, genetically modifying them, then giving them back to the person. This therapy is called gene transfer using anti-KRAS G12V mTCR cells. Objective: To see if anti-KRAS G12 V mTCR cells are safe and can shrink tumors. Eligibility: Adults at least 18 years old with cancer that has the KRAS G12V molecule on the surface of tumors. Design: In another protocol, participants will: Be screened Have cells harvested and grown Have leukapheresis In this protocol, participants will have the procedures below. Participants will be admitted to the hospital. Over 5 days, participants will get 2 chemotherapy medicines as an infusion via catheter in the upper chest. A few days later, participants will get the anti-KRAS G12V mTCR cells via catheter. For up to 3 days, participants will get a drug to make the cells active. A day after getting the cells, participants will get a drug to increase their white blood cell count. This will be a shot or injection under the skin. Participants will recover in the hospital for 1-2 weeks. They will have lab and blood tests. Participants will take an antibiotic for at least 6 months. Participants will have visits every few months for 2 years, and then as determined by their doctor. Visits will be 1-2 days. They will include lab tests, imaging studies, and physical exam. Some visits may include leukapheresis or blood drawn. Participants will have blood collected over several years.
A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients. --- G12V ---
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients Background: A new cancer therapy involves taking white blood cells from a person, growing them in the lab, genetically modifying them, then giving them back to the person. --- G12V ---
This therapy is called gene transfer using anti-KRAS G12V mTCR cells. --- G12V ---
Eligibility: Adults at least 18 years old with cancer that has the KRAS G12V molecule on the surface of tumors. --- G12V ---
A few days later, participants will get the anti-KRAS G12V mTCR cells via catheter. --- G12V ---
- INCLUSION CRITERIA: - Measurable metatstatic unresectable malignancy expressing G12V 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. --- G12V ---
Patients shown to have tumors expressing G12V mutated NRAS and HRAS will also be eligible as these oncogenes share complete amino acid homology with G12V mutated KRAS for their first 80 N-terminal amino acids, completely encompassing the target epitope. --- G12V ---
Patients shown to have tumors expressing G12V mutated NRAS and HRAS will also be eligible as these oncogenes share complete amino acid homology with G12V mutated KRAS for their first 80 N-terminal amino acids, completely encompassing the target epitope. --- G12V --- --- G12V ---
Patients who are receiving any other investigational agents - INCLUSION CRITERIA: - Measurable metatstatic unresectable malignancy expressing G12V 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. --- G12V ---
Patients who are receiving any other investigational agents Pancreatic Cancer Gastric Cancer Gastrointestinal Cancer Colon Cancer Rectal Cancer Pancreatic Neoplasms Gastrointestinal Neoplasms Background: - We generated an HLA-A*11:01-restricted murine T-cell receptor (mTCR) that specifically recognizes the G12V-mutated variant of KRAS (and other RAS family genes), expressed by many human cancers and constructed a single retroviral vector that contains its alpha and beta chains that confers recognition of this antigen when transduced into PBL. --- G12V ---
Objectives: Primary objectives: - Phase I: determine the safety of administering PBL transduced with anti-KRAS G12V mTCR in concert with preparative lymphodepletion and high dose interleukin-2 (IL-2; aldesleukin). --- G12V ---
- Phase II:To determine if anti-KRAS G12V mTCR-transduced PBL can mediate the regression of tumors harboring the RAS G12V mutation. --- G12V ---
- Phase II:To determine if anti-KRAS G12V mTCR-transduced PBL can mediate the regression of tumors harboring the RAS G12V mutation. --- G12V --- --- G12V ---
Eligibility: Patients must be/have: - Age greater than or equal to 18 years and less than or equal to 70 years - HLA-A*11:01 positive - Metastatic or unresectable RAS G12V-expressing cancer which has progressed after standard therapy (if available). --- G12V ---
Design: - This is a Phase I/II, single center study of PBL transduced with anti-KRAS G12V mTCR in HLA-A*11:01 positive patients with advanced solid tumors expressing G12V 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. --- G12V ---
Design: - This is a Phase I/II, single center study of PBL transduced with anti-KRAS G12V mTCR in HLA-A*11:01 positive patients with advanced solid tumors expressing G12V 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. --- G12V --- --- G12V ---
- Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-KRAS G12V mTCR. --- G12V ---
- On day 0 patients will receive their PBL transduced with the anti-KRAS G12V mTCR and will then begin high-dose aldesleukin. --- G12V ---
- 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 pancreatic cancer and Cohort 2b: all other RAS G12V non-pancreatic cancers - A total of 110 patients may be required; approximately 24 patients in the phase I portion of the study and 86 (41, plus an allowance of up to 2 non-evaluable per phase II cohort) patients in the phase II portion of the study. --- G12V ---
Description: Percentage of patients who have a clinical response to treatment (objective tumor regression)
Measure: Response rate Time: 6 and 12 weeks after cell infusion, then every 3 months x3, every 6 months x2 years, then per PI discretionDescription: Highest dose at which less than or equal to 1 of 6 patients experienced a DLT or the highest dose level studied if DLTs are not observed at any of the dose levels.
Measure: Maximum Tolerated Cell Dose (MTD) Time: Before progression to next higher dose levelDescription: TCR and vector presence will be quantitated in PBMC samples using established PCR techniques
Measure: In vivo survival of mTCR gene engineered cells Time: Batched and assayed at the conclusion of the studyThe 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.
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 --- --- G12V ---
Description: Area under the ROC curve of the mutation percentage obtained from plasma ccfDNA analysis
Measure: Area under ROC curve Time: 12 monthThe 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.
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 ---
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.
T-cell receptor (TCR) clonality and diversity in the periphery and tumor.. Inclusion Criteria: Part 1 Only - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D --- --- G12V ---
Part 2 Only - Has a histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), adenocarcinoma of the colon or rectum, or pancreatic adenocarcinoma, central laboratory confirmed Human Leukocyte Antigen (HLA) (HLA-A*11 and/or HLA-C*08 allele and mutated KRAS 4MUT+ (G12D, G12V, G13D or G12C) who have received, or been intolerant to or ineligible for all treatment known to confer clinical benefit) All - A male participant must agree to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period. --- G12D --- --- G12V ---
Inclusion Criteria: Part 1 Only - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D --- --- G12V ---
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 monthsDescription: 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 monthsDescription: 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 monthsDescription: Presence of and changes in the quantity of mutant KRAS specific T cells in the periphery.
Measure: Mutant KRAS Specific T cells Time: Up to approximately 24 monthsDescription: T-cell receptor (TCR) clonality and diversity in the periphery and tumor.
Measure: T-cell receptor (TCR) Time: Up to approximately 24 monthsThis research study is designed to evaluate the effects of a dendritic cell (kind of white blood cell) vaccine for pancreatic cancer.
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 --- --- G12V ---
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.
Stratification for KRAS mutation (G12V versus G12C versus other). --- G12V ---
outcome between G12V versus G12C versus other subtypes of KRAS mutations (mutational analysis on plasma and blood platelets).. --- G12V ---
The two most common KRAS types are G12C in about 40% of cases, G12V in 18% and G12D in 15% of cases. --- G12C --- --- G12V ---
Stratification for KRAS mutation (G12V versus G12C versus other) at randomization.. response by Crabb criteria (if applicable). --- G12V ---
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.