Johnson & Johnson pasritamig–JNJ-9401 combo yields 73% PSA50 response in Phase 1 mCRPC

Study results

First-in-human Phase 1 data presented at SITC 2026 show that at the recommended regimen 11 of 15 patients (73%) achieved ≥50% PSA reductions and 7 of 15 (47%) achieved ≥90% reductions; four patients reached undetectable PSA. All seven patients with ≥90% reductions remained on treatment for more than six months without disease progression. Patients at the recommended regimen were heavily pretreated (median four prior systemic therapies, range two to six).

Safety

At the recommended regimen there were no Grade 3 or higher treatment-related adverse events, no dose-limiting toxicities, and no treatment-related discontinuations or deaths reported in this early analysis. Cytokine release syndrome occurred in three patients (20%), all Grade 1 and presenting as transient fever; none required tocilizumab. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported.

Regimen and trial status

The recommended dosing is JNJ-9401 200 mg administered subcutaneously every six weeks combined with pasritamig 300 mg administered intravenously every six weeks, following two initial weekly pasritamig step-up doses, enabling outpatient administration. As of June 15, 2026, 144 patients had enrolled in the ongoing open-label, multicenter Phase 1 (NCT06095089). The combination is being evaluated in the Phase 3 KLK2-comPAS study (NCT07164443).

Mechanism and context

Pasritamig is a KLK2xCD3 bispecific T-cell engager designed to direct T cells to prostate cancer cells; JNJ-9401 is a PSMAxCD28 costimulatory bispecific intended to provide a complementary signal to strengthen and sustain T-cell activity. The regimen is the first clinical evaluation of a dual-tumor-antigen targeted bispecific antibody combination in prostate cancer.