Pasritamig Plus JNJ-9401 Yields 73% PSA Response in Metastatic CRPC

The investigational combination of pasritamig (JNJ-78278343), a first-in-class KLK2xCD3 bispecific T-cell engager, and JNJ-9401 (JNJ-87189401), a PSMAxCD28 costimulatory bispecific antibody, reduced prostate-specific antigen (PSA) levels by at least 50% in 73% of heavily pretreated patients with metastatic castration-resistant prostate cancer (CRPC), according to a news release from Johnson & Johnson.¹ Findings from the ongoing phase 1 trial (NCT06095089) were presented by Laura Graham, MD, during a late-breaking oral session at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting.²

What were the results of the pasritamig and JNJ-9401 trial?

Among the 15 patients treated at the recommended regimen, PSA reductions of at least 50% occurred in 73% (n = 11/15), and reductions of at least 90% occurred in 47% (n = 7/15). Four patients achieved undetectable PSA levels. All 7 patients with a PSA reduction of at least 90% remained on treatment without disease progression for more than 6 months. These patients had received a median of 4 prior lines of systemic therapy (range, 2-6).

The company stated that the findings are preliminary, are based on a small number of patients, and require further evaluation

“Prostate cancer has long been difficult to treat with immunotherapy,” said Graham, an assistant professor of medicine–medical oncology at the University of Colorado School of Medicine, in the press release. She added that the depth of responses, including those lasting 6 months or longer, provides early evidence supporting a larger phase 3 study.

What was the safety profile of the combination?

No grade 3 or higher treatment-related adverse events, dose-limiting toxicities, treatment-related discontinuations, or treatment-related deaths were reported at the recommended regimen. Cytokine release syndrome occurred in 20% of patients (n = 3/15); all cases were grade 1, presenting as temporary fever, and none required tocilizumab (Actemra). No cases of immune effector cell–associated neurotoxicity syndrome were reported.

What is the design of the phase 1 trial?

The open-label, multicenter, phase 1 trial enrolled patients with metastatic CRPC who had received at least 1 prior systemic therapy. In part 1, investigators escalated the dose of JNJ-9401 with a fixed dose of pasritamig to assess safety and identify the recommended regimen. Dose expansion is ongoing at that regimen and includes a cohort of patients with first-line metastatic CRPC. As of June 15, 2026, 144 patients had enrolled.

The recommended regimen consists of JNJ-9401 at 200 mg administered subcutaneously every 6 weeks plus pasritamig at 300 mg administered intravenously every 6 weeks, following 2 weekly step-up doses of pasritamig. Treatment is administered in the outpatient setting.

How are pasritamig and JNJ-9401 designed to work?

According to the developers, the combination is the first dual tumor antigen–targeted bispecific antibody regimen evaluated clinically in prostate cancer. Pasritamig binds KLK2 on prostate cancer cells and CD3 on T cells, delivering the primary signal that directs T cells to the tumor, and it previously showed single-agent antitumor activity in a phase 1 study. JNJ-9401 binds PSMA and the costimulatory receptor CD28, providing a second signal intended to strengthen and sustain T-cell activity.

What is next for pasritamig in metastatic CRPC?

Pasritamig with or without JNJ-9401 is being evaluated vs placebo in late-line metastatic CRPC in the phase 3 KLK2-comPAS study (NCT07164443). Pasritamig plus docetaxel is also being compared with docetaxel alone in the first-line metastatic CRPC setting in the phase 3 KLK2-PASenger trial (NCT07225946).

References

1. Johnson & Johnson reports 73% PSA response rate with investigational pasritamig-based immunotherapy combination in advanced prostate cancer. News release. Johnson & Johnson. November 8, 2026. Accessed November 9, 2026. https://tinyurl.com/25rrpuxs
2. Graham LS, Massard C, Rasco DW, et al. Combining PSMA×CD28 costimulatory T-cell engager (TCE) JNJ-87189401 with pasritamig (KLK2×CD3): first-in-human phase 1 results of a dual-antigen targeted TCE regimen in prostate cancer. Presented at: 2026 Society for Immunotherapy of Cancer (SITC) Annual Meeting; November 4-8, 2026; Phoenix, AZ. Abstract LBA 1175.