FDA Clears IND for ADI-212, a PSMA-Targeted CAR T, in mCRPC

The FDA has cleared the investigational new drug (IND) application for ADI-212, an allogeneic gamma-delta (γδ) chimeric antigen receptor (CAR) T-cell therapy targeting prostate-specific membrane antigen (PSMA), for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), according to a news release.¹ The sponsor plans to initiate phase 1 enrollment in the fourth quarter of 2026.

The planned study (NCT07793435) is a phase 1/2, multicenter, open-label, dose-finding and dose-expansion trial of ADI-212 in adults with PSMA-positive mCRPC.²

“Designed as a single off-the-shelf product, ADI-212 incorporates multiple platform enhancements by combining gene-editing and the expression of novel immune-stimulating molecules intended to strengthen anti-tumor potency, including improved antigen engagement, capacity for durable tumor-killing and active modulation of tumor microenvironment,” Blake Aftab, PhD, chief scientific officer of Adicet Bio, stated in the news release.¹

Mechanism and Design Enhancements

ADI-212 is an ‘off-the-shelf’ next-generation, gene-edited, armored γδ Vδ1 CAR T-cell therapy engineered to express a novel CAR binder designed to enhance tolerability and tumor-specific recognition of PSMA. According to the release, the program combines membrane-tethered interleukin-12 armoring with CRISPR/Cas9-mediated knockout of mediator complex subunit 12 (MED12), an approach that could improve potency in solid tumors and enable multiple antitumor mechanisms within the tumor microenvironment.

Preclinical Rationale

Preclinical findings presented at the 32nd Annual Prostate Cancer Foundation Scientific Retreat showed the CAR T-cell therapy’s PSMA-specific expression that minimizes the potential for systemic toxicities, and its ability to expand and deliver cytotoxic activity despite the presence of suppressive Treg cells.³ In comparison to PSMA CAR αβ T cells, it showed enhanced cytotoxicity vs in vitro 22Rv1 tumor cells and a favorable cytokine profile.

In PSMA-expressing PC3 xenograft models in NOD scid gamma mice, a single intravenous dose of ADI-212 produced durable tumor growth control, including at a reduced stress-test dose, and demonstrated antitumor activity against both a primary tumor and a contralateral flank tumor rechallenge administered 15 days after initial inoculation.

Trial Design

The planned phase 1/2 trial will use a 3+3 design in an initial dose-escalation cohort to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) and the recommended phase 2 dose (RP2D), followed by a dose-expansion cohort at the RP2D to assess antitumor activity. Patients in both cohorts will receive ADI-212 by infusion following lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The trial is currently planned for a single site in Redwood City, California; estimated enrollment is 12 patients, with an estimated study start of September 2026 and primary completion of October 2028.

Patients must have progressive mCRPC based on prostate-specific antigen, soft-tissue progression, or bone disease progression, with PSMA-avid target lesions. They must have at least 2 prior courses of androgen deprivation therapy and no more than 1 prior taxane. They can have received prior PARP inhibitor therapy and a single course of PSMA-targeted radioligand therapy, but no other PSMA-targeted therapies and no prior CAR T-cell therapy.

The primary end points are MTD/MAD and the proportion of treatment emergent and treatment-related adverse events; overall response rate per PCWG3-modified RECIST v1.1 and radiographic progression-free survival will also be reported.

REFERENCES

1. Adicet Bio Announces FDA Clearance of IND Application for ADI-212. News release. Adicet Bio, Inc. August 27, 2026. Accessed August 28, 2026. https://tinyurl.com/3bc2nzzt

2. A phase 1/2 trial of ADI-212 in mCRPC. ClinicalTrials.gov. Updated August 28, 2026. Accessed August 28, 2026. https://clinicaltrials.gov/study/NCT07793435

3. Herrman M, Murthy P, Ding B, et al. ADI-212: a next-generation gene-edited and armored allogeneic CAR γδ T cell therapy targeting PSMA for prostate cancer. Poster presented at: Prostate Cancer Foundation Scientific Retreat; October 25, 2025. https://tinyurl.com/muk6eefe