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

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.