Dr Graham on Data for JNJ-87189401 Plus Pasritamig in mCRPC

The most exciting thing to me is that we're starting to see deep, durable, and sustained PSA responses with this immunotherapy approach [in mCRPC].

Laura Graham, MD, an assistant professor of medicine in the Division of Medical Oncology at the University of Colorado School of Medicine and a genitourinary medical oncologist at the UCHealth Tony Grampsas Urologic Cancer Care Clinic, discussed first-in-human phase 1 data (NCT06095089) evaluating the PSMA x CD28 costimulatory T-cell engager JNJ-87189401 (JNJ-9401) plus the KLK2 x CD3 bispecific T-cell engager pasritamig (JNJ-78278343) in metastatic castration-resistant prostate cancer (mCRPC).

In data presented at the 2026 SITC Annual Meeting, patients treated at the recommended phase 2 regimen (RP2R; n = 15) received intravenous pasritamig at 300 mg every 6 weeks after step-up dosing, plus subcutaneous JNJ-87189401 at 200 mg every 6 weeks starting on day 15. They received a median of 4 prior lines of therapy (range, 2-6), including taxane chemotherapy (66.7%) and radioligand therapy (66.7%).

At the RP2R, no grade 3 or higher treatment-related adverse effects, dose-limiting toxicities, or treatment-related discontinuations or deaths occurred, Graham said. Cytokine release syndrome occurred in 20.0% of patients; all events were grade 1, limited to fever, and none required tocilizumab (Actemra). No immune effector cell–associated neurotoxicity syndrome was observed, and 2 patients (13%) had grade 1 elevated alanine aminotransferase/aspartate aminotransferase levels that resolved without intervention, she noted.

At the 2 highest JNJ-87189401 doses (400 mg and 800 mg), investigators saw high-grade but reversible hepatic toxicity. According to Graham, dose optimization supported 200 mg as the safest and most effective dose, as higher doses did not increase activity.

At the RP2R, 73.3% achieved a PSA decline of at least 50% (PSA50), and 46.7% experienced a decline of at least 90% (PSA90). Four patients (26.7%) reached an undetectable PSA level (<0.2 ng/mL), which Graham described as very uncommon in heavily pretreated mCRPC; all 4 remained in response for more than 6 months, with responses ongoing at data cutoff. Responses trended deeper in nonvisceral disease (n = 11), with PSA50 and PSA90 rates of 82% and 54%, respectively. At a median follow-up of 7.4 months, median radiographic progression-free survival was not reached in this group (95% CI, 5.88-not estimable).

Pasritamig with or without JNJ-87189401 is under evaluation in the phase 3 KLK2-comPAS trial (NCT07164443) in late-line mCRPC.