Johnson & Johnson reports 73% PSA response with pasritamig and JNJ-9401 in Phase 1 mCRPC study, with 47% achieving PSA reductions of at least 90%.
Written By: Malavatu Satvika, PharmD
Reviewed By: Pharmacally Editorial Team
Johnson & Johnson reported first-in-human Phase 1 findings for its investigational combination of pasritamig and JNJ-9401, with 73% of patients achieving Prostate-Specific Antigen (PSA) reductions of at least 50% at the recommended regimen. Among the 15 patients evaluated, seven (47%) achieved reductions of at least 90%, including four who reached undetectable PSA levels. The findings were presented at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting (Abstract LBA 1175) on November 8, 2026.
The combination is being investigated in metastatic castration-resistant prostate cancer (mCRPC), an advanced disease setting in which treatment options become increasingly limited following progression despite androgen pathway-directed therapies. By combining KLK2-directed T-cell engagement with PSMA-directed costimulation, the approach aims to strengthen T-cell activity against prostate cancer cells.
Trial Design and Patient Population
The ongoing, open-label, multicentre Phase 1 study (NCT06095089) is evaluating the safety and preliminary clinical activity of pasritamig plus JNJ-9401 in patients with mCRPC who have received at least one prior systemic therapy. The study includes dose escalation and expansion.
As of June 15, 2026, 144 patients had enrolled in the study. The reported efficacy findings are from 15 patients treated at the recommended Phase 2 regimen. These patients had received a median of four prior lines of systemic therapy (range, two to six), indicating substantial previous treatment exposure. The 73% PSA response rate therefore applies to this small recommended-regimen group, not the overall study population.
The combination uses two complementary mechanisms to stimulate T-cell activity. Pasritamig is a KLK2×CD3 bispecific antibody that directs T cells towards prostate cancer cells expressing kallikrein-related peptidase 2 (KLK2). JNJ-9401 is a PSMA×CD28 costimulatory bispecific antibody that targets prostate-specific membrane antigen (PSMA) and provides an additional signal intended to enhance T-cell activation and function.
This dual-antigen-targeted approach is designed to combine tumour-directed T-cell engagement with costimulation, addressing two components of the immune response within a single treatment regimen.
Deep PSA Responses and Early Durability
At the recommended regimen, 11 of 15 patients (73%) achieved PSA reductions of at least 50%, while seven (47%) achieved reductions of at least 90%. Four patients (27%) reached undetectable PSA levels, defined as below 0.2 ng/mL.
All seven patients achieving PSA reductions of at least 90% remained on treatment for more than six months without disease progression. The four patients with undetectable PSA levels also maintained responses beyond six months, with responses ongoing at the June 15, 2026 data cutoff.
These findings indicate substantial biochemical responses in a heavily pretreated population. However, PSA is a biomarker used to monitor prostate cancer activity. Its reduction does not independently establish radiographic tumour response, improved progression-free survival or longer overall survival. The observations therefore represent an early signal of biological activity rather than confirmed clinical benefit.
Safety and Recommended Regimen
At the recommended regimen, treatment-related adverse events occurred in 46.7% of patients. No Grade 3 or higher treatment-related adverse events, serious treatment-related events, dose-limiting toxicities, treatment-related discontinuations or treatment-related deaths were reported.
Cytokine release syndrome (CRS) occurred in three patients (20%). All cases were Grade 1, presented as transient fever and did not require tocilizumab. No immune effector cell-associated neurotoxicity syndrome (ICANS) was reported. Two patients (13%) experienced reversible Grade 1 elevations in alanine aminotransferase and aspartate aminotransferase.
The recommended regimen combines JNJ-9401 200 mg subcutaneously every six weeks, starting on Day 15, with pasritamig 300 mg intravenously every six weeks following two initial weekly pasritamig step-up doses. The schedule supports the potential for outpatient administration, although its safety and tolerability require evaluation in larger populations.
Phase 3 Development and Clinical Implications
The combination is being evaluated in the Phase 3 KLK2-comPAS study (NCT07164443), which is investigating pasritamig with or without JNJ-9401 against placebo, with best supportive care in the respective treatment arms. Overall survival is the primary endpoint.
The Phase 3 programme will provide a more definitive assessment of whether adding PSMA-directed CD28 costimulation to KLK2-directed T-cell engagement improves clinical outcomes compared with the control strategies.
The early findings are notable for the depth of PSA reductions and their persistence among patients receiving the recommended regimen. Nevertheless, the efficacy analysis involves only 15 patients, and the Phase 1 study is open-label and non-comparative. The absence of severe treatment-related adverse events in this subgroup also does not establish the long-term safety of the combination.
The central question for further development is whether these deep biochemical responses translate into improved disease control and survival. The Phase 3 KLK2-comPAS study will be important in determining the clinical value of this dual-bispecific strategy in advanced prostate cancer.
References
Johnson & Johnson. Johnson & Johnson Reports 73% PSA Response Rate with Investigational Pasritamig-Based Immunotherapy Combination in Advanced Prostate Cancer. November 8, 2026.
Graham LS, et al. Combining PSMA×CD28 costimulatory T-cell engager JNJ-87189401 with pasritamig (KLK2×CD3): first-in-human Phase 1 results of a dual-antigen-targeted TCE regimen in prostate cancer. SITC 2026; Abstract LBA 1175.
A Study of JNJ-87189401 Combined With JNJ-78278343 for Advanced Prostate Cancer, ClinicalTrials.gov ID NCT06095089
A Study of Pasritamig with or Without JNJ-87189401 Versus Placebo for Late Line Metastatic Castration-resistant Prostate Cancer (mCRPC) (KLK2-comPAS), ClinicalTrials.gov ID NCT07164443
About the Writer
Malavatu Satvika (Linkedin) is a Pharm.D professional and aspiring healthcare medical writer with clinical exposure and research experience. Her interests include medical writing, drug safety, pharmaceutical research, and evidence-based healthcare communication. She has contributed to two research publications in pharmaceutical journals and has gained practical experience in prescription review, patient counselling, medication review, adverse drug reaction monitoring, drug information services, literature review, and clinical documentation through regular hospital training.
She has completed certifications in clinical research, ICH-GCP E6(R3), data management for clinical research, and congenital hypothyroidism. With a strong foundation in pharmacy, clinical practice, and scientific research, she aims to translate complex medical and pharmaceutical information into accurate, clear, and evidence-based healthcare content. She is also preparing to pursue a PhD and further develop her expertise in medical writing and pharmaceutical research.