ADI-212 Receives FDA IND Clearance for Castration-Resistant Prostate Cancer

The FDA has cleared the investigational new drug (IND) application for ADI-212, an off-the-shelf, gene-edited allogeneic gamma delta 1 chimeric antigen receptor (CAR) T cell therapy targeting prostate-specific membrane antigen (PSMA), for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC), according to a news release from the developer, Adicet Bio.¹ They plan to initiate enrollment in a phase 1 trial (NCT07793435) evaluating the agent in patients with metastatic CRPC in the fourth quarter of 2026.

What is ADI-212 and how does it work?

ADI-212 is designed to target PSMA, which is highly expressed across prostate cancer cells including those that are castration-resistant. As an allogeneic, off-the-shelf product derived from gamma delta 1 T cells, ADI-212 does not require patient-specific manufacturing, a key practical distinction from autologous CAR T approaches.

The agent incorporates 3 distinct platform enhancements intended to improve anti-tumor activity in the solid tumor setting. A novel CAR binder is incorporated to enhance tolerability and tumor-specific recognition. Membrane-tethered interleukin-12 (IL-12) armoring is designed to stimulate immune activity directly within the tumor microenvironment. CRISPR/Cas9-mediated disruption of subunit 12 of the mediator complex (MED12) is intended to improve CAR T cell persistence and function by countering immunosuppressive signals.

"ADI-212 marks an important milestone in Adicet's strategy to address the complexity of solid tumors and represents an important addition to our portfolio of allogeneic gamma delta 1 cell therapies and in vivo CAR T programs," stated Blake Aftab, PhD, chief scientific officer of Adicet Bio, in the news release.¹ "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."

What is the planned ADI-212 phase 1 trial design in metastatic CRPC?

Eligibility criteria for the phase 1/2 trial includes histologically or cytologically confirmed adenocarcinoma of the prostate, evidence of metastatic disease, presence of PSMA-avid target lesions by PET/CT, and progressive metastatic CRPC histology. Patients in the phase 1/2 trial will undergo treatment in a dose escalation and dose expansion cohort. In the dose escalation cohort, ADI-212 will be given via infusion using a 3 + 3 design across 3 dose levels to determine the maximum tolerated dose or maximum assessed dose. In the dose expansion cohort, patients will undergo treatment at the recommended phase 2 dose. In addition to ADI-212, patients will receive chemotherapy consisting of fludarabine or cyclophosphamide for lymphodepletion.

What is the unmet need in metastatic castration-resistant prostate cancer?

Patients with metastatic CRPC face limited options after progressing on androgen receptor pathway inhibitors (ARPIs), and novel therapeutic strategies remain a clinical priority in this population. PSMA has emerged as a validated target in metastatic CRPC, underscored by the 2022 FDA approval of lutetium-177 vipivotide tetraxetan (Pluvicto) in PSMA-positive disease after prior ARPI and taxane-based chemotherapy.

While CAR T cell therapies have substantially transformed outcomes in hematologic malignancies, achieving comparable efficacy in solid tumors has remained challenging due to immunosuppressive tumor microenvironments, tumor antigen heterogeneity, and inadequate CAR T cell trafficking and persistence. The design of ADI-212, combining IL-12 armoring and CRISPR-mediated MED12 disruption, is intended to address these specific barriers within the prostate cancer tumor microenvironment.

What is ADI-212's role in Adicet Bio's solid tumor pipeline?

ADI-212 represents Adicet's first oncology program targeting prostate cancer and its second solid tumor candidate overall, alongside ADI-270, an anti-CD70 gamma delta 1 CAR T cell therapy in a phase 1 study for patients with relapsed/refractory clear cell renal cell carcinoma (ccRCC; NCT06480565).³ Preclinical studies of ADI-212 showed enhanced activity compared with prior-generation alpha-beta and gamma delta CAR T programs in oncology, according to the developers.

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/3579hnd4
2. A phase 1 study of ADI-212 in metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Updated August 28, 2026. Accessed August 28, 2026. https://tinyurl.com/mwy5hyax
3. A phase 1/2 trial of ADI-270 in ccRCC. ClinicalTrials.gov. Updated August 15, 2025. Accessed August 28, 2026. https://tinyurl.com/3tjm87nh