Can a new immunotherapy combination help the immune system fight advanced prostate cancer more effectively? Johnson & Johnson has reported promising early results from an investigational combination of two bispecific antibodies, pasritamig and JNJ-9401, with 73% of patients achieving a significant reduction in prostate-specific antigen (PSA) levels in a Phase 1 clinical study.
The findings were presented during a late-breaking oral session at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting. The combination is designed to activate and strengthen the body’s immune response against prostate cancer by targeting two different proteins found on cancer cells.
Dual-targeted immunotherapy activates T cells against cancer
The investigational combination targets two prostate cancer proteins: kallikrein-related peptidase 2 (KLK2) and prostate-specific membrane antigen (PSMA). It uses complementary signals to activate T cells, which play an important role in identifying and attacking cancer cells.
Pasritamig, a bispecific antibody targeting KLK2 and CD3, directs T cells towards prostate cancer cells. Meanwhile, JNJ-9401 targets PSMA and CD28, providing an additional signal designed to enhance T-cell activation and function. Together, these antibodies aim to generate a stronger and more sustained immune response against cancer.
Study reports 73% PSA reduction among patients
The Phase 1 study evaluated the combination in patients with metastatic castration-resistant prostate cancer (mCRPC), an advanced form of the disease that continues to progress despite treatments targeting the androgen receptor pathway.
Among the 15 patients who received the recommended treatment regimen, 11 (73%) achieved PSA reductions of at least 50%. Furthermore, seven patients (47%) experienced reductions of at least 90%, while four achieved undetectable PSA levels.
Notably, all seven patients who achieved PSA reductions of at least 90% remained on treatment for more than six months without disease progression. These findings indicate promising early antitumour activity, although further studies are needed to establish the combination’s clinical benefits.
Combination demonstrates encouraging safety profile
The investigational combination also demonstrated an encouraging safety profile in the early analysis. Researchers reported no Grade 3 or higher treatment-related adverse events, dose-limiting toxicities, or treatment-related events leading to treatment discontinuation or death.
Cytokine release syndrome (CRS), an inflammatory reaction that can occur following T-cell activation, was observed in three patients (20%). However, all cases were mild (Grade 1), involving temporary fever, and none required treatment with tocilizumab. Researchers also reported no cases of immune effector cell-associated neurotoxicity syndrome (ICANS).
The recommended regimen involves JNJ-9401 administered subcutaneously every six weeks alongside intravenous pasritamig every six weeks, following two initial weekly step-up doses. This schedule indicates the potential for administering the combination in an outpatient setting.
Combination advances to Phase 3 clinical evaluation
Building on these encouraging Phase 1 findings, Johnson & Johnson is advancing the combination into the Phase 3 KLK2-comPAS study (NCT07164443). The trial will evaluate whether adding JNJ-9401 to pasritamig can improve outcomes for patients with metastatic castration-resistant prostate cancer.
The company is also investigating pasritamig alone and in combination with other therapies across advanced prostate cancer. However, the current findings are based on a small group of 15 patients receiving the recommended regimen, and larger clinical studies will be necessary to confirm the treatment’s safety and effectiveness.
As reported by prnewswire.com, Johnson & Johnson announced these promising Phase 1 findings on November 8, 2026, highlighting the potential of dual-antigen-targeted immunotherapy combinations in advancing treatment approaches for advanced prostate cancer.