A Phase II Study of Adjuvant Immunotherapy Targeting KRAS G12D, KRAS G12V, or TP53 R175H for Participants With Advanced Gastrointestinal Malignancies

Summary

Background:

Gastrointestinal (GI) cancer affects the organs (such as the stomach, large and small intestine, pancreas, colon, liver, and biliary system) of the digestive tract. In some participants who have had surgery for GI cancer, blood tests show that the cancer has spread despite being unable to be identified by scans. Certain gene mutations (changes) in GI cancer (such as KRAS or TP53) can be targeted by T cells, a type of immune cell, in individuals with specific HLA types (genes that help proteins in the body know what is self and non-self). Researchers want to see if they can stop GI cancer from returning or spreading in people with these gene mutations and specific HLA types.

Objective:

To test therapy with modified T-cells to prevent or delay the return of GI cancer after standard treatment. T-cells play a role in the body s immune system.

Eligibility:

People aged 18 to 72 years with GI cancer that was treated with standard therapy and is not seen on imaging scans. They must have specific gene mutations and HLA types. They also must have certain clinical or blood tests showing the cancer is spreading (elevating CA19-9 or detectable ctDNA).

Design:

Participants will be divided into 2 groups. Participants nor the study team can choose what Group to participate in; this is done by randomization , like flipping a coin. Participants will have a 1-to-1 chance of being in Group 1 or Group 2.

Group 1 will receive T-cell therapy. Their own T-cells will be collected. In a lab, the cells will be combined with a virus that carries a protein to target cancer cells.

Group 1 participants will stay in the hospital for 3 weeks or more. They will have chemotherapy, and their modified T-cells will be infused through a tube attached to a needle inserted into a vein.

Group 1 participants will visit the clinic every 3 months for 1 year and then every 6 months for 5 years. Then they will have follow-up visits for another 10 years under a different protocol.

Group 2 participants will not receive treatment with T-cells. They will visit the clinic every 3 months for 1 year and then every 6 months for 5 years.

Conditions

• Gastrointestinal Carcinoma
• Pancreatic Cancer
• Hepatocellular Cancer
• Cholangiocarcinoma
• Duodenal Cancer
• Colorectal Cancer
• Small Bowel Cancer
• Metastatic Cancers

Interventions

BIOLOGICAL

KRAS TCR-Transduced PBL

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

DRUG

Aldesleukin

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 3 days (maximum 3 doses)

DRUG

Fludarabine

Days -7 to -3: Fludarabine 25 mg/m\^2/day IVPB daily over 30 minutes for 4 days

DRUG

Cyclophosphamide

Days -7 and -6: Cyclophosphamide 30 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 7.5 mg/kg/day over 1 hour x 2 days

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Nicholas D Klemen, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

72 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-09

Primary Completion

2025-09-09

Completion

2025-09-09

FDA Drug

Yes

Countries

• United States

Study Locations