At the American Association for Cancer Research (AACR) 2025 Annual Meeting, researchers unveiled updated results from a Phase 1/2 clinical trial (NCT03972657 which is still recruiting) testing a novel treatment for metastatic castration-resistant prostate cancer (mCRPC). The combination of nezastomig (REGN5678), a bispecific antibody, and cemiplimab, an immune-boosting drug, showed encouraging tumor-shrinking effects and extended survival, but serious side effects raised red flags.
The trial, involving 78 men who had exhausted at least two prior treatments, tested weekly doses of nezastomig (0.1 to 300 mg) alongside cemiplimab (350 mg every three weeks). At higher doses (30 mg or more), 25% of patients saw their PSA levels—a key marker of prostate cancer—drop by at least 50%, with 16% achieving a 90% reduction. These patients lived a median of 17.3 months, compared to 10.3 months for those on lower doses. Tumor growth was also delayed longer at higher doses (5.0 months vs. 2.1 months).
However, the treatment’s immune-activating approach came with risks. Three-quarters of patients experienced side effects like fatigue, nausea, or cytokine release syndrome. More concerning, 14% suffered severe immune-related reactions, including two deaths from complications linked to overactive immune responses. These risks were most common in patients who responded best to the treatment, suggesting a complex link between efficacy and toxicity.

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Clinical trial.