J&J’s Dual-Antigen Bispecific Regimen Achieves 73% PSA Response in Advanced Prostate Cancer

Johnson & Johnson’s investigational combination of two bispecific antibodies, pasritamig and JNJ-9401, reduced prostate-specific antigen (PSA) levels by at least 50% in 73% of patients (11 of 15) with metastatic castration-resistant prostate cancer (mCRPC) treated at the recommended regimen in a first-in-human phase 1 study.¹ Seven of the 15 patients (47%) achieved PSA reductions of at least 90%, and four reached undetectable PSA levels.¹ The results were presented in a late-breaking oral session at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting.¹

“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, who has provided consulting, advisory, and speaking services to Johnson & Johnson.¹

How does the combination work?

The company describes the regimen as the first dual-tumor-antigen-targeted bispecific antibody regimen clinically evaluated in prostate cancer.¹ Pasritamig is a first-in-class bispecific that binds kallikrein-related peptidase 2 (KLK2) on prostate cancer cells and CD3 on T cells, providing the first signal that directs T cells to the tumor.¹ KLK2 is expressed on prostate cancer cells with limited expression in normal tissue.² JNJ-9401 binds prostate-specific membrane antigen (PSMA) and CD28, a costimulatory receptor on T cells, to deliver a second signal designed to strengthen and sustain T-cell activity.¹

The design builds on a long-established principle of immunology: full T-cell activation generally requires both an antigen-specific signal through the T-cell receptor and a costimulatory signal, with CD28 serving as the primary costimulatory receptor.³

Targeting two tumor-associated proteins also reflects a broader push for more precise bispecific design. In a BioPharm International® video interview, Atul Mohindra, then head of biologics R&D at Lonza, said, “The need for increasing precision medicine [and] reducing off target events is always going to be there.”

Why is prostate cancer a hard target for immunotherapy?

While immunotherapies have transformed treatment for several cancers, immune checkpoint inhibitors have shown minimal clinical benefit in prostate cancer.⁴ Patients with mCRPC face limited options as their disease progresses, with median overall survival of approximately two to three years.¹

What did the trial show?

As of June 15, 2026, 144 patients had enrolled in the ongoing, open-label, multicenter study.¹ Patients treated at the recommended regimen were heavily pretreated, with a median of four prior lines of systemic therapy.¹ All seven patients with PSA reductions of at least 90% remained on treatment for more than six months without disease progression.¹

At the recommended regimen, no Grade 3 or higher treatment-related adverse events, dose-limiting toxicities, or treatment-related discontinuations or deaths were reported.¹ Cytokine release syndrome occurred in three patients (20%), all Grade 1 and presenting as temporary fever, and none required tocilizumab.¹ No cases of immune effector cell-associated neurotoxicity syndrome were reported.¹ The company cautioned that the findings are based on a small number of patients and require confirmation in a larger population.¹

The recommended regimen pairs JNJ-9401 200 mg, given subcutaneously every six weeks, with pasritamig 300 mg, given intravenously every six weeks after two weekly step-up doses, a schedule the company said could be administered in an outpatient setting.¹

The combination results compare with earlier pasritamig data, although cross-trial comparisons are limited. In the phase 1 monotherapy study, 42.4% of 33 evaluable patients at the recommended phase 2 dose achieved a PSA reduction of at least 50%, and median radiographic progression-free survival was 7.85 months.²˒⁵ Earlier this year, BioPharm International reported that pasritamig plus docetaxel produced a 64.7% PSA50 response rate in 51 patients.

What happens next?

The combination is being evaluated in the phase 3 KLK2-comPAS study (NCT07164443), which is testing pasritamig with or without JNJ-9401 against placebo in later-line mCRPC.¹˒⁶ A second phase 3 study, KLK2-PASenger, is evaluating pasritamig plus docetaxel in first-line mCRPC.¹

“With this combination now in phase 3 development, we are building on the early promise of this approach as we work to bring new treatment options to patients with advanced disease,” said Yusri Elsayed, MD, MHSc, PhD, global therapeutic area head, oncology, at Johnson & Johnson.¹

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.
2. Pasritamig displays safety, durable disease control in heavily pretreated mCRPC. OncLive. Published July 14, 2025. Accessed November 9, 2026.
3. Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of T cell costimulation. Annu Rev Immunol. 1996;14:233-258. doi:10.1146/annurev.immunol.14.1.233
4. Rai V. Immune checkpoint inhibitor therapy for prostate cancer: present and future prospectives. Biomolecules. 2025;15(6):751. doi:10.3390/biom15060751
5. Stein MN, Vinceneux A, Robbrecht D, et al. Pasritamig, a first-in-class, bispecific T-cell engager targeting human kallikrein 2, in metastatic castration-resistant prostate cancer: a phase I study. J Clin Oncol. 2025;43(22):2515-2526. doi:10.1200/JCO-25-00678
6. A study of pasritamig with or without JNJ-87189401 versus placebo for late line metastatic castration-resistant prostate cancer (mCRPC) (KLK2-comPAS). ClinicalTrials.gov identifier: NCT07164443. Updated 2026. Accessed November 9, 2026.