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

Intermediate-size Patient Population IND for Treatment of Patients With Advanced Cancer Using T Cells Engineered to Express T-cell Receptors (TCR) Targeting Mutant KRAS

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.

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.