Immunotherapy has largely failed prostate cancer patients, but a Phase 1 dataset presented at SITC this week gives that effort its clearest signal yet. Among 15 heavily pretreated men with metastatic castration-resistant prostate cancer treated at the recommended regimen of pasritamig plus JNJ-9401, 73 percent achieved PSA reductions of at least 50 percent, and nearly half (47 percent) hit reductions of at least 90 percent, including four patients who reached undetectable levels. Those patients had received a median of four prior lines of therapy, making the depth of response harder to dismiss as low-hanging fruit.
The design behind the numbers is what makes this worth watching. Pasritamig targets KLK2, a prostate-specific protein, and provides the first T-cell activation signal; JNJ-9401 targets PSMA and delivers a second, complementary signal to sustain T-cell activity. J&J describes this as the first dual-tumor-antigen-targeted bispecific antibody regimen evaluated clinically in prostate cancer, and the Phase 1 data suggest the two-signal approach is doing something single-agent checkpoint blockade has consistently failed to do in this disease. Checkpoint inhibitors have shown minimal clinical benefit in the broader mCRPC population, leaving the broader population without an effective immunotherapy option.
The safety read at this early stage is also practically relevant. No Grade 3 or higher treatment-related adverse events appeared at the recommended regimen. Cytokine release syndrome, the main concern with T-cell engagers, occurred in 20 percent of patients at the recommended regimen, all Grade 1 fever that resolved without tocilizumab. The dosing schedule, subcutaneous JNJ-9401 and intravenous pasritamig every six weeks after two initial weekly step-up doses of pasritamig, is designed for outpatient administration. All seven patients who achieved at least a 90 percent PSA reduction remained on treatment for more than six months without progression, which matters for a disease where median overall survival in mCRPC ranges from roughly 13.5 to 31.6 months depending on the site and extent of disease.
The combination has already moved into the Phase 3 KLK2-comPAS study (NCT07164443), which asks whether adding JNJ-9401 to pasritamig improves outcomes versus pasritamig alone in mCRPC. The number to watch from that trial is radiographic progression-free survival: PSA is a useful early signal, but it is what happens to disease on imaging that will determine whether this two-signal strategy translates into a regulatory conversation.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
