RecruitingPhase 1NCT06253520

Autologous T-cells Genetically Engineered to Express Receptors Reactive Against KRAS Mutations in Conjunction With a Vaccine Directed Against These Antigens in Participants With Metastatic Cancer

A Phase Ib Clinical Trial to Evaluate the Administration of Autologous T-cells Genetically Engineered to Express Receptors Reactive Against KRAS Mutations in Conjunction With a Vaccine Directed Against These Antigens in Participants With Metastatic Cancer

Sponsor

National Cancer Institute (NCI)

Enrollment

210 participants

Start Date

May 16, 2024

Study Type

INTERVENTIONAL

Conditions

Breast Cancer Colorectal, Cancer Ovarian Cancer Non-small Cell Lung Cancer Gastrointestinal Cancer Metastatic Solid Cancers Genitourinary Cancer

Summary

Background: Many cancer cells produce substances called antigens that are unique to each cancer. These antigens stimulate the body s immune responses. One approach to treating these cancers is to take disease-fighting white blood cells from a person, change those cells so they will target the specific proteins (called antigens) from the cancer cells, and return them to that person s blood. The use of the white blood cells in this manner is one form of gene therapy. A vaccine may help these modified white cells work better. Objective: To test a cancer treatment that uses a person s own modified white blood cells along with a vaccine that targets a specific protein. Eligibility: Adults aged 18 to 72 years with certain solid tumors that have spread after treatment. Design: Participants will undergo leukapheresis: Blood is removed from the body through a tube attached to a needle inserted into a vein. The blood passes through a machine that separates out the white blood cells. The remaining blood is returned to the body through a second needle. Participants will stay in the hospital for 3 or 4 weeks. They will take chemotherapy drugs for 1 week to prepare for the treatment. Then their modified white cells will be infused through a needle in the arm. They will take other drugs to prevent infections after the infusion. The vaccine is injected into a muscle; participants will receive their first dose of the vaccine on the same day as their cell infusion. Participants will have follow-up visits 4, 8, and 12 weeks after the cell infusions. They will receive 2 or 3 additional doses of the boost vaccine during these visits. Follow-up will continue for 5 years, but participants will need to stay in touch with the gene therapy team for 15 years. ...

Eligibility

Min Age: 18 YearsMax Age: 72 Years

Plain Language Summary

Simplified for easier understanding

This National Cancer Institute trial tests a highly personalized cell therapy for people with solid tumors (such as colon, lung, breast, or ovarian cancer) carrying a specific mutation called KRAS G12V or G12D. Researchers take the patient's own T-cells (immune cells), genetically engineer them to recognize and attack cancer cells with this mutation, and infuse them back into the patient. **You may be eligible if...** - You have a confirmed solid tumor (e.g., colorectal, lung, breast, ovarian) with a KRAS G12V or G12D mutation - Your cancer has not responded to standard treatments - You have the right genetic 'match' (HLA type) for the engineered T-cells available at this study - Your cancer diagnosis was confirmed by the NCI Laboratory of Pathology **You may NOT be eligible if...** - You have not yet tried standard treatments for your cancer type - You do not have the required HLA type to match the available T-cell receptors - You have other conditions making the treatment unsafe Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGAldesleukin

Aldesleukin 600,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 10 doses). Patients in Cohort 3 may receive 72,000 IU/kg IV.

DRUGFludarabine

Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

DRUGCyclophosphamide

Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.

BIOLOGICALKRAS TCR-Transduced PBL

Day 0: Cells will be infused intravenously (IV) over 20-30 minutes (2-4 days after the last dose of fludarabine).

BIOLOGICALGRT-C903/GRT-R904

Day 0 (GRT-C903): Injection of 1.0 mL at each of 2 bilateral vaccine injections. Weeks 4, 8 and 12 (as applicable, GRT-R904): Injection of 0.25 mL of diluted GRT-R904 at each of 2 bilateral vaccine injections