A first-in-human Phase I study presented at the Society for Immunotherapy of Cancer annual meeting found that Johnson & Johnson’s dual-bispecific regimen drove deep PSA declines in metastatic castration-resistant prostate cancer: 11 of 15 patients (73%) achieved PSA50, and 7 patients achieved PSA90 responses that have lasted more than 6 months without progression. The combination pairs pasritamig, a KLK2/CD3 bispecific, with JNJ-9401, a PSMA/CD28 costimulatory bispecific, and showed no grade 3 or higher treatment-related adverse events at the recommended dose.

Why It Matters To Oncology

• The data offer an early clinical signal that dual-bispecific immune engagement may deepen and sustain responses in mCRPC, a setting still in need of new mechanisms beyond androgen receptor pathway inhibitors, taxanes, and radioligand therapy.

• Mechanistically, pasritamig redirects T cells to KLK2-expressing prostate cancer cells, while JNJ-9401 adds a CD28 costimulatory signal intended to enhance T-cell activation and function.

• At the recommended regimen, four patients reached undetectable PSA levels, suggesting the combination may be capable of inducing particularly deep responses in a subset of patients.

The Financials

• Johnson & Johnson did not disclose new deal or financing terms alongside the SITC update.

• The company is already investing in late-stage prostate cancer development, including the Phase III KLK2-comPAS study of pasritamig alone and with JNJ-9401 in mCRPC.

• J&J is also running the KLK2-PASenger trial evaluating pasritamig plus docetaxel in first-line mCRPC, underscoring broader franchise commitment in prostate cancer.

What They're Saying

• J&J said the findings support an outpatient-friendly schedule: two initial weekly pasritamig step-up doses, followed by subcutaneous JNJ-9401 200 mg and intravenous pasritamig 300 mg every 6 weeks.

• The company reported no dose-limiting toxicities, no treatment-related discontinuations or deaths, and no immune effector cell-associated neurotoxicity syndrome at the recommended dose.

• Cytokine release syndrome occurred in 3 patients, with all events grade 1.

What's Next

• Key questions now are whether the PSA responses translate into radiographic progression-free survival and overall survival benefits in larger studies.

• Clinicians and drug developers will also watch for durability, patient-selection biomarkers, and whether the safety profile holds as exposure broadens.

• Readouts from Phase III development should clarify whether this dual-bispecific strategy can become a new backbone in mCRPC treatment.

Reference: J&J's bispecific combo shows early promise in prostate cancer study