Intermediate-size IND for Treatment of Patients With Advanced Cancer Using T Cells Engineered to Express TCR Targeting Mutant KRAS

N/ATemporarily Not AvailableNCT07614048

Providence Health & Services

Overview

The goal of this intermediate-size expanded access treatment program is to treat a subset of patients with advanced solid cancers, specifically pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), that express KRAS-G12D and the appropriate HLA with adoptive t-cell therapy. Participants will provide leukapheresis product which will be processed and generated in our facility. The participant's peripheral blood T cells will be stimulated and then transduced with GMP-grade retroviral vectors encoding KRAS-G12D-neoantigen reactive TCR. On Days -6 to -4, the participant will receive outpatient chemotherapy as a preparative regimen. On Day 0, participant will receive cell product infusion as an inpatient procedure. Following infusion, participant will receive supportive care through discharge.

As the eligible population is extremely limited, geographically dispersed, and insufficient to support timely enrollment into a traditional clinical trial, the investigators believe expanded access via an intermediate size IND represents the only practical mechanism to provide potentially beneficial investigational therapy to patients with this rare molecular profile who lack alternative therapeutic options.

Study Type

EXPANDED_ACCESS

Conditions

PDAC - Pancreatic Ductal Adenocarcinoma Colorectal Cancer

Interventions

CyclophosphamideDRUG

Patients will receive 300 mg/m2/day IV cyclophosphamide as part of a conditioning regimen on Days -6 to -4.

FludarabineDRUG

Patients will receive 30 mg/m2/day fludarabine as part of a conditioning regimen on Days -6 to -4.

Cell infusionBIOLOGICAL

Cells will be administered at a dose of between 1x109 to 1x1010 TCR-T cells. If manufactured product does not meet target range, product may still be administered with Investigator discretion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically confirmed, advanced or metastatic solid tumor with a documented KRAS G12D mutation confirmed by a CLIA-certified assay, and a high-resolution HLA typing demonstrating expression of HLA-A11:01 and/or HLA-C08:02. * Disease-specific prior therapy requirements: 1. Advanced colorectal cancer: prior treatment with fluoropyrimidine-based chemotherapy regimens with exposure to both oxaliplatin and irinotecan. 2. Advanced pancreatic ductal adenocarcinoma: prior treatment with at least one systemic regimen, including either a fluoropyrimidine-based regimen (e.g., FOLFIRINOX), or a gemcitabine-based regimen (gemcitabine with nab-paclitaxel, or gemcitabine with cisplatin). 3. Advanced non-small cell lung cancer: prior receipt of at least one line of therapy including a PD-1 or PD-L1 inhibitor, with or without platinum-based chemotherapy. 4. Advanced esophageal/gastroesophageal/gastric adenocarcinoma: patients are required to have received at least one line of fluoropyrimidine-based chemotherapy. For tumors harboring HER2 amplifications, prior treatment with at least one HER2-targeted therapy is required. For tumors with combined positive score (CPS) or 1 or higher, prior treatment with immune checkpoint inhibitor is required. 5. Advanced small bowel adenocarcinoma: patients are required to have received fluoropyrimidine-based chemotherapy regimens containing oxaliplatin and irinotecan. 6. Advanced appendiceal adenocarcinoma: patients are required to have received fluoropyrimidine-based chemotherapy regimens containing oxaliplatin and irinotecan. 7. Advanced biliary tract adenocarcinoma and periampullary adenocarcinoma: patients are required to have received at least one prior line of therapy. For tumors with FGFR2 fusions, a prior exposure to an FGFR inhibitor is required.

Data from ClinicalTrials.gov

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