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

The FDA has cleared the investigational new drug (IND) application for ADI-212 for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC), according to a news release from Adicet Bio, the therapy’s developer.¹ ADI-212 is an off-the-shelf, gene-edited allogeneic Vδ1 chimeric antigen receptor (CAR) T-cell therapy targeting prostate-specific membrane antigen (PSMA). Adicet Bio plans to initiate enrollment in the fourth quarter of 2026 in a phase 1 trial (NCT07793435) evaluating the agent in patients with metastatic CRPC.

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 Vδ1 T cells, ADI-212 does not require patient-specific manufacturing, which is a key practical distinction from autologous CAR T approaches.

The agent incorporates 3 distinct platform enhancements intended to improve antitumor activity in the solid tumor setting. A novel CAR binder is incorporated to enhance tolerability and tumor-specific recognition. Membrane-tethered IL-12 armoring is designed to stimulate immune activity directly within the tumor microenvironment. CRISPR/Cas9-mediated disruption of 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 Vδ1 cell therapies and in vivo CAR T programs," Blake Aftab, PhD, chief scientific officer of Adicet Bio, said 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 antitumor 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 CRPC?

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 Lu 177 vipivotide tetraxetan (Pluvicto) in PSMA-positive disease after prior ARPI and taxane-based chemotherapy.

Although 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/Cas9-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 Bio's first oncology program targeting prostate cancer and its second solid tumor candidate overall, alongside ADI-270, an anti-CD70 Vδ1 CAR T-cell therapy in a phase 1 study for patients with relapsed/refractory clear cell renal cell carcinoma (NCT06480565).³ Preclinical studies of ADI-212 showed enhanced activity compared with prior-generation αβ and γδ 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. August 27, 2026. Accessed August 28, 2026. https://tinyurl.com/3579hnd4
2. A phase 1/2 trial of ADI-212 in mCRPC. 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