Overview
- A first‑in‑human phase 1 study tested a PSMA×CD28 costimulatory engager (JNJ‑87189401) given subcutaneously with a KLK2×CD3 bispecific (pasritamig) given intravenously in late‑line metastatic castration‑resistant prostate cancer.
- At the recommended phase 2 regimen of JNJ‑87189401 200 mg SC every 6 weeks plus pasritamig 300 mg IV every 6 weeks, 73.3% of patients achieved at least a 50% PSA decline and 46.7% achieved at least a 90% decline, with four patients reaching undetectable PSA and remaining in response at data cutoff.
- Safety at the RP2R was manageable with no grade 3 or higher treatment‑related events, no dose‑limiting toxicities, and grade 1 cytokine release syndrome in 20% of patients; higher JNJ‑87189401 doses caused reversible immune‑mediated liver injury that supported selecting 200 mg.
- The trial cohort was heavily pretreated (median four prior lines, two‑thirds had prior taxane and radioligand therapy) and responses were deeper in patients without visceral disease, while median radiographic progression‑free survival was not reached with ongoing follow‑up.
- Janssen has advanced pasritamig with or without JNJ‑87189401 into the phase 3 KLK2‑comPAS trial to test whether the deep PSA signals translate into confirmed clinical benefit and longer survival, and translational data showed increased CD8 T‑cell proliferation and interleukin‑2 consistent with the intended costimulatory mechanism.