Phase I/II Study of Autologous T Cells to Express T-Cell Receptors (TCRs) in Subjects With Solid Tumors

A Phase I/II study of autologous T cells engineered using the Sleeping Beauty transposon/transposase system to express TCR(s) reactive against neoantigens in subjects with relapsed/refractory solid tumors. Screening was initially conducted under TCR001-002. TCR001-201 Protocol Amendment 4, approved by the IRB on 20 January 2023 and implemented at the site in February 2023, incorporated HLA typing and tumor neoantigen screening into TCR001-201. Eligibility required a matching tumor mutation and HLA restriction represented in the Sponsor's clinical TCR library. The Phase I part of this study is a prospective, open-label, dose-escalation study of TCR-T cell drug product in patients with progressive or recurrent solid tumors who have failed standard therapy. The Phase II part is a prospective, open-label, single dose portion of the study. The planned Phase II portion was to begin after determination of the maximum tolerated dose or recommended Phase II dose in Phase I. The program closed during Phase I Arm A before that determination. Arm B and Phase II were not initiated, and no subject received interleukin-2 under this study. Subjects with one of the following histologically confirmed solid tumors will be included: * Cohort 1: Gynecologic cancer (e.g., ovarian, endometrial) * Cohort 2: Colorectal cancer * Cohort 3: Pancreatic cancer * Cohort 4: Non-small cell lung cancer (NSCLC); NSCLC includes but is not limited to squamous cell carcinoma, adenosquamous carcinoma or adenocarcinomas * Cohort 5: Cholangiocarcinoma Subject must have a tumor mutation and HLA typing combination that matches to at least one of the following TCRs in the Alaunos' library (mutation \& HLA type): * KRAS G12D \& HLA-A\*11:01 * KRAS G12D \& HLA-C\*08:02 * KRAS G12V \& HLA-A\*11:01 * KRAS G12V \& HLA-C\*01:02 * TP53 R175H \& HLA-A\*02:01 * TP53 R175H \& HLA-DRB1\*13:01 * TP53 R248W \& HLA-A\*68:01 * TP53 Y220C \& HLA-A\*02:01 * TP53 Y220C \& HLA-DRB3\*02:02 * EGFR E746-A750del \& HLA-DPA1\*02:01, DPB1\*01:01