Redwood City-based Adicet Bio (Nasdaq: ACET) has registered a Phase I/II trial of ADI-212, an allogeneic gamma delta chimeric antigen receptor (CAR) T cell therapy targeting prostate-specific membrane antigen (PSMA), in adults with metastatic castration-resistant prostate cancer (mCRPC). The registration follows FDA clearance of the investigational new drug (IND) application, announced in August 2026, with the company stating it plans to initiate enrollment in Q4 2026. The trial is listed as not yet recruiting (NCT07793435).
The multicenter, open-label Phase I/II study will enroll up to 12 adults with PSMA-positive mCRPC. Part 1 uses a 3+3 dose-escalation design to determine the maximum tolerated or assessed dose and recommended Phase II dose, followed by an expansion cohort evaluating anti-tumor activity. Primary endpoints include dose-limiting toxicities and treatment-emergent adverse events, with overall response rate and radiographic progression-free survival among secondary measures. Patients receive ADI-212 after fludarabine/cyclophosphamide lymphodepletion. Primary completion is expected in October 2028.
ADI-212 is an off-the-shelf allogeneic Vδ1 gamma delta T cell product engineered with a novel CAR binder targeting PSMA, membrane-tethered interleukin-12 (mbIL-12) armoring to modulate the immunosuppressive tumor microenvironment, and CRISPR/Cas9-mediated disruption of MED12 (Mediator complex subunit 12) to improve T cell persistence and anti-tumor potency, according to Adicet. Preclinical data presented at the 32nd Annual Prostate Cancer Foundation Scientific Retreat in October 2025 demonstrated enhanced cytotoxicity against PSMA-expressing castration-resistant prostate cancer cell lines and durable tumor control in xenograft rechallenge models, the company stated. The Vδ1 subset is not MHC-restricted, which the company said reduces graft-versus-host disease risk in allogeneic settings and may support tumor tissue penetration.
Novartis's lutetium Lu 177 vipivotide tetraxetan (Pluvicto), a PSMA-targeted radioligand therapy, received an expanded US FDA approval in July 2026 for PSMA-positive metastatic androgen pathway modulation-naïve or -sensitive prostate cancer following the PSMAddition trial. California-based MultiValent Biotherapies is advancing MVB-101, a bivalent peptide-like drug conjugate targeting both PSMA and folate receptor alpha (FRα) with an MMAE payload, into a Phase Ib/IIa trial expected to begin in Q3 2026. ADI-212 is differentiated by its cellular mechanism — delivering cytotoxic T cell activity rather than radiation or cytotoxic payload — and its allogeneic, off-the-shelf manufacturing model, which Adicet has said is intended to enable broad patient access without the lead time of autologous CAR T manufacturing.