Phase 1/2 ADI-212 PSMA-targeted γδ (Vδ1) CAR-T cells in mCRPC.

This Phase 1/2 multicenter, open-label, dose-escalation (3+3) and dose-expansion study evaluates ADI-212, an allogeneic engineered γδ (Vδ1) CAR-T cell therapy that targets PSMA on prostate cancer cells, sponsored by Adicet Therapeutics. Participants receive lymphodepleting chemotherapy with fludarabine (a purine analog that inhibits DNA synthesis) and cyclophosphamide (an alkylating agent that crosslinks DNA), followed by a single infusion of ADI-212, with escalation aimed at defining the maximum tolerated/maximally assessed dose and expansion assessing anti-tumor activity at the recommended Phase 2 dose. The eligible population is adults with relapsed/refractory metastatic castration-resistant prostate cancer that is PSMA-positive/PSMA-avid (PSMA expression is common in advanced prostate cancer, and PSMA PET selection enriches for targetable disease). A key angle is the “off-the-shelf” γδ CAR-T approach in a solid tumor, where manufacturing speed and tumor-microenvironment resistance are major bottlenecks for autologous αβ CAR-T programs. Today’s care for mCRPC is continued androgen deprivation plus sequential systemic options such as AR-pathway inhibitors, taxane chemotherapy, PARP inhibitors for HRR-mutated disease, radiopharmaceuticals like lutetium-177–PSMA for eligible patients, and supportive bone-directed therapy—so this trial tests whether PSMA-directed cellular therapy can deliver deeper responses after standard lines have failed.