Pasritamig combination yields 73% PSA response rate in phase 1 mCRPC study

The investigational combination of pasritamig and JNJ-9401 demonstrated preliminary antitumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC), according to findings from a phase 1 study presented at the 2026 Society for Immunotherapy of Cancer (SITC) Annual Meeting.¹

Among 15 patients treated at the recommended regimen, 11 (73%) achieved a prostate-specific antigen (PSA) reduction of at least 50%, and 7 (47%) achieved a PSA reduction of at least 90%. All 7 patients with PSA reductions of at least 90% remained on treatment for more than 6 months without disease progression.

The combination pairs pasritamig, a KLK2 × CD3 bispecific T-cell engager, with JNJ-9401, a PSMA × CD28 costimulatory bispecific antibody. The regimen represents a dual-antigen-targeted approach to T-cell activation in advanced prostate cancer.

"Prostate cancer has long been difficult to treat with immunotherapy, which makes the activity we're seeing particularly interesting," said Laura Graham, MD, assistant professor of medicine–medical oncology at the University of Colorado School of Medicine, in a news release from Johnson & Johnson.¹ "By combining two complementary approaches to T-cell activation, we are exploring a new way to engage the immune system against this disease. The depth of PSA reductions observed in this study, including responses sustained for 6 months or longer, provides encouraging early evidence for the pasritamig-JNJ-9401 combination that warrants further investigation in a larger Phase 3 study."

Phase 1 study findings and safety

The ongoing phase 1 study (NCT06095089) is an open-label, multicenter trial evaluating the safety and preliminary clinical activity of pasritamig plus JNJ-9401 in patients with mCRPC who have received at least 1 prior systemic therapy. The dose-escalation portion evaluated JNJ-9401 alongside fixed-dose pasritamig, with safety and determination of the recommended regimen as primary objectives. Dose expansion subsequently included patients receiving the recommended regimen, as well as a frontline mCRPC cohort.

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

As of June 15, 2026, 144 patients had enrolled in the study. Fifteen patients were included in the recommended-regimen efficacy analysis had received a median of 4 prior lines of systemic therapy (range, 2 to 6), reflecting a heavily pretreated population.

Among those 15 patients, 73% (11 of 15) achieved a PSA reduction of at least 50%, and 47% (7 of 11) achieved PSA reductions of at least 90%. Four patients achieved undetectable PSA levels. All 7 patients with PSA reductions of at least 90% remained on treatment for more than 6 months without disease progression.

No grade 3 or higher treatment-related adverse events (TRAEs) were reported in this group. With the recommended regimen, 3 patients (20%) experienced CRS, with all cases classified as grade 1 and presenting as transient fever. None required tocilizumab. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported. Investigators also reported no dose-limiting toxicities, treatment-related discontinuations, or treatment-related deaths in this cohort.

Phase 3 evaluation

The combination is being further assessed in mCRPC in the ongoing phase 3 KLK2-comPAS trial (NCT07164443). The randomized, double-blind trial is evaluating pasritamig with or without JNJ-9401, alongside best supportive care, compared with placebo plus best supportive care in patients with late-line mCRPC.²

Related: KLK2-comPAS trial explores dual T-cell engagement in mCRPC

The trial plans to enroll over 1200 participants across all cohorts. Overall survival is a primary efficacy measure. Additional efficacy end points include radiographic progression-free survival, time to symptomatic progression, time to skeletal-related events, and time to PSA progression.

In addition to this trial, pasritamig is also being evaluated in combination with docetaxel in the phase 3 KLK2-PASenger study in first-line mCRPC.

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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://www.jnj.com/media-center/press-releases/johnson-johnson-reports-73-psa-response-rate-with-investigational-pasritamig-based-immunotherapy-combination-in-advanced-prostate-cancer

2. A Study of Pasritamig With or Without JNJ-87189401 Versus Placebo for Late Line Metastatic Castration-resistant Prostate Cancer (mCRPC) (KLK2-comPAS). ClinicalTrials.gov. Last updated November 3, 2026. Accessed November 9, 2026. https://clinicaltrials.gov/study/NCT07164443