TAC T-cells for the Treatment of Claudin 18.2 Positive Solid Tumors (TACTIC-3)

The TAC technology is a novel approach to modifying T cells, herein referred to as TAC T cells, and using them in the treatment of solid tumors. TAC T cells are produced through genetic engineering, incorporating TAC receptors into a patient's own T cells. This redirects these enhanced T cells to specific cancer antigens, and upon recognition, activates them through the natural signaling pathways of the endogenous TCR. In the TAC01-CLDN18.2 engineered T cell product; TAC T cells recognize the CLDN18.2, a tight junction protein present on the surface of tumor cells, where the protein expression is no longer limited to tight junctions and are visible to T cells to eradicate them. Consequently, it is hypothesized TAC01-CLDN18.2 will be potentially safe and active in treating patients with CLDN18.2+ solid tumors and provide a clinically meaningful therapeutic benefit in patient populations with high unmet medical need. This is a first-in-human study investigating TAC01-CLDN18.2 to evaluate the safety, MTD or RP2D, PK, and efficacy in subjects with CLDN18.2+ solid tumors who have been treated with at least 2 lines of prior therapy in Phase 1 and after at least 2 lines and no more than 4 lines of prior therapy in Phase 2 (Note: in each phase, subjects with PDAC may have been treated with 1 line of prior antineoplastic therapy. In addition, subjects who are being treated with current lines of therapy, but not deriving benefit or not tolerating therapy, and have not progressed maybe also eligible as long as they have measurable disease at baseline as a starting reference point). In Phase 1, escalating doses of TAC01-CLDN18.2 will be evaluated to identify the RP2D using the classic 3+3 dose escalation study design. In Phase 2, dose expansion groups will further evaluate the efficacy, safety, and PK of the MTD or RP2D for TAC01-CLDN18.2 in subjects with gastric and esophageal AC (Group A), PDAC (Group B), and mucinous ovarian and NSCLC cancers (Group C). In Phase 2, definitions of eligible CLDN18.2+ IHC expression levels will be based on analysis of data from Phase 1 for signals of clinical activity since there are no formal CAP/ASCO guidelines for CLDN18.2+ expression levels. In Phase 2, a Simon 2-stage design will be used to enroll up to 57 subjects in Group A and 22 subjects in Group C. Group B (PDAC) will enroll up to 10 subjects as an exploratory cohort due to the historically low ORRs observed in PDAC. The 10 treated subjects in Group B are designed to seek evidence of potential clinical activity in this difficult to treat CLDN18.2+ subpopulation of PDAC.