Overview
Phase I Study, a master protocol to investigate TCR-Engineered T cells recognizing KRAS mutations in adult subjects with Unresectable, Advanced, and/or Metastatic Solid Tumors.
Description
This is a Phase 1, open-label, Phase 1, Multi-Center Master Protocol to evaluate the safety and preliminary Anti-Tumor activity of TCR-Engineered T cells (KRAS TCRTs) recognizing KRAS mutations in adult subjects with Unresectable, Advanced, and/or Metastatic Solid Tumors.
Eligibility
Key Inclusion Criteria:
- Age ≥18 years
- Diagnosed with NSCLC, Colorectal adenocarcinoma, Pancreatic adenocarcinoma, Endometrial Cancer or any other solid tumor
- Tumors must harbor a KRAS G12D variant mutation and subject must be HLA-C\08:02 positive, HLA-A\11:01 or HLA-A\*11:02 positive in at least one allele
- Subject has advanced solid cancer, defined as unresectable, advanced, and/or metastatic disease (Stage III or IV) after at least 1 line of approved systemic standard of care (SOC) treatment regimen and for which there are no available curative treatment options.
- Presence of at least 1 measurable lesion per RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment
Key Exclusion Criteria:
- Any other primary malignancy within the 3 years prior to enrollment (except for non-melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or low-grade prostate cancer
- Known, active primary central nervous system (CNS) malignancy
- History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation.
- History of stroke or transient ischemic attack within the 12 months prior to enrollment.
- History of clinically significant cardiac disease within the 6 months prior to enrollment or heart failure at any time prior to enrollment.
- Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter, prior to enrollment.
- Any form of primary immunodeficiency.
- Active immune-mediated disease requiring systemic steroids or other immunosuppressive treatment (except if related to prior checkpoint inhibitor therapy)
- Female of childbearing potential who is lactating or breast feeding at the time of enrollment
- Prior treatment with pan-KRAS or KRAS G12D targeting agents unless presence of KRAS G12D mutation is confirmed after the completion of treatment with pan-KRAS or KRAS G12D targeting agents.