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.

NCT03190941

Conditions

1. Pancreatic Cancer
2. Gastric Cancer
3. Gastrointestinal Cancer
4. Colon Cancer
5. Rectal Cancer

Interventions

1. Drug: Cyclophosphamide
2. Drug: Fludarabine
3. Biological: Anti-KRAS G12V mTCR PBL
4. Drug: Aldesleukin

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 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 ---

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. - 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 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 RAS G12V pancreatic cancer, and Cohort 2b, patients with RAS G12V non-pancreatic cancer. --- 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 RAS G12V pancreatic cancer, and Cohort 2b, patients with RAS G12V non-pancreatic cancer. --- G12V --- --- G12V ---

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 --- --- G12V ---

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 ---

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 --- --- G12V ---

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 --- --- G12V ---

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 --- --- G12V ---

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

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

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. --- G12V ---

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. --- G12V --- --- G12V ---

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. --- G12V --- --- G12V --- --- G12V ---

- Patient's tumor must express the KRAS G12V mutation, or a G12V mutation in HRAS or NRAS, as determined by DNA or RNA sequencing methods. --- G12V ---

- Patient's tumor must express the KRAS G12V mutation, or a G12V mutation in HRAS or NRAS, as determined by DNA or RNA sequencing methods. --- G12V --- --- G12V ---

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 --- --- G12V ---

The investigators will test the safety and activity of adoptive transfer of autologous T cells genetically engineered to express a TCR that targets mutant KRAS G12V in the context of HLA-A*11:01 in HLA-matched patients with advanced pancreatic cancer that express mutant KRAS G12V. --- G12V ---

The investigators will test the safety and activity of adoptive transfer of autologous T cells genetically engineered to express a TCR that targets mutant KRAS G12V in the context of HLA-A*11:01 in HLA-matched patients with advanced pancreatic cancer that express mutant KRAS G12V. --- G12V --- --- G12V ---

This study will assess the safety and efficacy of VS-6766 monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer.

NCT04620330

Conditions

1. Non Small Cell Lung Cancer
2. KRAS Activating Mutation

Interventions

1. Drug: VS-6766
2. Drug: VS-6766 and Defactinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

A Study of VS-6766 v. VS-6766 + Defactinib in Recurrent G12V or Other KRAS-Mutant Non-Small Cell Lung Cancer This study will assess the safety and efficacy of VS-6766 monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer. --- 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.

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

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 ---