T Cell Receptor T Cells for Advanced KRAS G12V-mutant Non-small Cell Lung Cancer, Pancreas Cancer, Colon Cancer

Brief summary public domain (ClinicalTrials.gov)

This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ transgenic T cells expressing high affinity KRASG12V mutation-specific T cell receptors (FH-A11KRASG12V-TCR) and to see how well they work in treating patients with solid tumor cancers that has spread from where it first started (primary site) to other places in the body (metastatic). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize KRAS G12V, a protein on the surface of tumor cells. These KRAS G12V-specific T cells may help the body's immune system identify and kill KRAS G12V solid cancer tumor cells.

Detailed description public domain (ClinicalTrials.gov)

OUTLINE: This is a dose-escalation study of FHA11KRASG12V-TCR. Patients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with either cyclophosphamide intravenously (IV) and fludarabine IV on days -6, -5, and -4, or bendamustine IV on days -4 and -3 at the discretion of the treating clinician and/or principal investigator (PI). Patients then receive FHA11KRASG12V-TCR IV on day 0. Patients may receive an additional FHA11KRASG12V-TCR IV infusion as soon as 28 days or up to 1 year after the first infusion. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) as well as blood sample collection and a tissue biopsy at baseline and throughout the trial. After completion of study treatment, patients are followed up on day 56, 112, 168, 224, 280 and day 365, then long-term for up to 15 years.

Intervention public domain (ClinicalTrials.gov)

Drug: Bendamustine. Receive IV

Intervention public domain (ClinicalTrials.gov)

Procedure: Biopsy. Undergo tissue biopsy

Intervention public domain (ClinicalTrials.gov)

Procedure: Biospecimen Collection. Undergo blood sample collection

Intervention public domain (ClinicalTrials.gov)

Procedure: Computed Tomography. Undergo CT

Intervention public domain (ClinicalTrials.gov)

Drug: Cyclophosphamide. Receive IV

Intervention public domain (ClinicalTrials.gov)

Procedure: Echocardiography. Undergo ECHO

Intervention public domain (ClinicalTrials.gov)

Drug: Fludarabine. Receive IV

Intervention public domain (ClinicalTrials.gov)

Procedure: Leukapheresis. Undergo leukapheresis

Arm public domain (ClinicalTrials.gov)

Treatment (FHA11KRASG12V-TCR) (experimental): Patients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with either cyclophosphamide IV and fludarabine IV on days -6, -5, and -4, or bendamustine IV on days -4 and -3 at the discretion of the treating clinician and/or PI. Patients then receive FHA11KRASG12V-TCR IV on day 0. Patients may receive an additional FHA11KRASG12V-TCR IV infusion as soon as 28 days or up to 1 year after the first infusion. Patients undergo ECHO or MUGA during screening. Patients also undergo CT, PET or MRI as well as blood sample collection and a tissue biopsy at baseline and throughout the trial.

Primary outcome public domain (ClinicalTrials.gov)

Incidence of adverse events. Safety and tolerability should be evaluated after each infusion. Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0). Time frame: Within 1 year after 1st infusion of (autologous CD8+ and CD4+ transgenic T cells expressing high affinity KRASG12V mutation-specific T cell receptors (FH-A11KRASG12V-TCR).

Primary outcome public domain (ClinicalTrials.gov)

Dose-limiting toxicity rates. Will be assessed by treatment-related grade 3 or higher toxicity and assessed by NCI CTCAE v5.0. The treatment will be considered to have an acceptable safety profile if the observed toxicity rate is consistent with a true rate that does not exceed 35%. Time frame: From the time of lymphodepletion chemotherapy to 28 days after FH-A11KRASG12V-TCR infusion.

Primary outcome public domain (ClinicalTrials.gov)

Maximum tolerated dose of FH-A11KRASG12V-TCR. Will be assessed by NCI CTCAE v5.0. Time frame: From the time of lymphodepletion chemotherapy to 28 days after FH-A11KRASG12V-TCR infusion.

Primary outcome public domain (ClinicalTrials.gov)

Recommended phase 2 dose of FH-A11KRASG12V-TCR. Will be assessed by NCI CTCAE v5.0. Time frame: Within 1 year after 1st infusion of FH-A11KRASG12V-TCR.

Secondary outcome public domain (ClinicalTrials.gov)

Reproducibly generating FHA11KRASG12V- TCR from autologous participant cells (Feasibility). Time frame: Within 1 year after eligibility determination.

Secondary outcome public domain (ClinicalTrials.gov)

Overall response rate (ORR). Time frame: Within 1 year after 1st infusion of FH-A11KRASG12V-TCR.

Secondary outcome public domain (ClinicalTrials.gov)

Stable disease (SD). Time frame: Within 1 year after 1st infusion of FH-A11KRASG12V-TCR.

Secondary outcome public domain (ClinicalTrials.gov)

Clinical benefit rate (CBR). Time frame: Within 1 year after 1st infusion of FH-A11KRASG12V-TCR.

Secondary outcome public domain (ClinicalTrials.gov)

ORR. Time frame: Within 1 year after 1st infusion of FH-A11KRASG12V-TCR.

Secondary outcome public domain (ClinicalTrials.gov)

Progression-free survival. Time frame: From study registration to disease progression or death of any cause), assessed up to 1 year after 1st infusion of FH-A11KRASG12V-TCR.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * LEUKAPHERESIS: Diagnosis of metastatic solid tumor * LEUKAPHERESIS: Tissue confirmation of solid tumor. Confirmation of diagnosis must be or have been performed by internal pathology review of archival biopsy material or other pathologic material at Fred Hutch/University of Washington Cancer Consortium (UWMC) * LEUKAPHERESIS: HLA-A\*11:01 confirmed through HLA typing at a clinically accredited laboratory * LEUKAPHERESIS: Previously documented KRASG12V mutation in tumor or plasma cell-free deoxyribonucleic acid (cfDNA) specimens by polymerase chain reaction (PCR) or next-generation sequencing (NGS) test * LEUKAPHERESIS: Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm, unless lymph node in which case short axis must be ≥ 15 mm. Baseline imaging (for example, diagnostic CT chest/abdomen/pelvis and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) if clinically indicated, must be obtained within 8 weeks of the first planned T cell infusion. MRI can be substituted for CT in participants unable to have CT contrast * LEUKAPHERESIS: Participants must be willing to undergo tumor biopsy for research purposes if safe and feasible at baseline (prior to first T cell infusion), 2-3 weeks after the first T cell infusion, and approximately 2 weeks +/- 1 week after the 2nd infusion (if applicable), if safe and feasible (these time windows may vary due to manufacturing or clinical reasons). Should there be no tumor tissue that is accessible for biopsy, participants will still be considered for participation, at the discretion of the investigator. Similarly, should an investigator determine that a biopsy cannot be performed safely for clinical reasons, biopsies may be cancelled or rescheduled. Patients can also refuse biopsies at any time after enrollment * LEUKAPHERESIS: Participants must be at least two weeks or five half-lives (for small molecules) from last systemic treatment: At least 2 weeks must have passed since any: immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, vaccines), or chemotherapy cancer treatment. At least five half-lives must have passed from treatment with small molecules or other investigational agents. There is no washout period for radiation, so long as radiated lesion is not the lesion being …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 24 participants (estimated).