Phase 1/2 Trial: REGN21353 Plus Nezastomig STEAP1×CD3 and PSMA×CD28 Combination Enters mCRPC Trials

A new phase 1/2 trial will test REGN21353, a STEAP1×CD3 bispecific antibody, alone and in combination with nezastomig (REGN5678), a PSMA×CD28 costimulatory bispecific, in previously treated metastatic castration-resistant prostate cancer mCRPC (metastatic androgen pathway modulation-resistant prostate cancer mAPMR). The approach combines two different prostate cancer antigens and two complementary immune signals: CD3-mediated T-cell activation through STEAP1 and CD28 costimulation through PSMA.

No clinical data for REGN21353 are available yet and the study has not started recruiting, so efficacy and safety remain completely unknown. However, the protocol offers some clues about the expected drug-class behaviour.

The biological rationale is supported by the broad expression of STEAP1 in prostate cancer and by previous clinical validation of STEAP1×CD3 targeting with xaluritamig. PSMA and STEAP1 are frequently co-expressed but not identical across metastatic lesions, meaning that using two tumour antigens could theoretically improve coverage and reduce opportunities for antigen escape.

The key questions will be whether the STEAP1×CD3/PSMA×CD28 combination can produce deeper or more durable responses than CD3 targeting alone, and whether this can be achieved without excessive immune toxicity.

Clinical trial.