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A novel two-drug combo is making headway against "immunologically cold" prostate cancer. In a phase 1 trial, JNJ-87189401 plus pasritamig achieved a 73% PSA50 response rate in heavily pretreated metastatic castration-resistant prostate cancer (mCRPC), with nearly half of patients hitting PSA90. Crucially, the regimen showed an excellent safety profile — no grade 3+ treatment-related adverse events at the recommended dose.
Prostate cancer has long been considered an "immunologically cold" tumor — meaning T cells rarely infiltrate it, making immunotherapy largely ineffective. But a new dual T-cell engager combination is changing that narrative. Results from a first-in-human phase 1 study presented at the 2026 SITC Annual Meeting show that combining JNJ-87189401 (a PSMA x CD28 costimulatory T-cell engager) with pasritamig (a KLK2 x CD3 bispecific T-cell engager) produced deep and durable PSA responses in patients with heavily pretreated mCRPC.
The combo works by delivering a one-two punch to T cells: pasritamig provides the first activation signal via CD3, while JNJ-87189401 adds a costimulatory boost through CD28 — essentially priming the immune system to attack prostate cancer cells more effectively.
By the Numbers:
Why it matters: These results are significant because late-line mCRPC patients have very few effective options remaining. The combination's strong efficacy signals — especially in patients without visceral disease — alongside a clean safety profile make it a compelling candidate for further development. A phase 3 trial (KLK2-comPAS) is already underway, comparing pasritamig with or without JNJ-87189401 vs. placebo, with overall survival as the primary endpoint.
