RARITAN, N.J., February 26, 2026
Johnson & Johnson (NYSE: JNJ) announced preliminary Phase 1b clinical results demonstrating promising antitumor activity for pasritamig (JNJ-78278343) in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). The investigational regimen delivered deep prostate-specific antigen (PSA) responses, durable disease control, and a favorable safety profile, supporting advancement into Phase 3 trials. Data were presented at the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, highlighting the potential of this first-in-class bispecific T-cell engager to expand the role of immunotherapy in advanced prostate cancer.
Deep PSA Responses in Heavily Pretreated Patients
The open-label Phase 1b study evaluated pasritamig in combination with docetaxel in 51 patients with mCRPC whose disease had progressed after androgen receptor pathway inhibitor therapy. Approximately 45% of patients had received at least one prior taxane regimen, with a median of three prior therapies overall. The study demonstrated clinically meaningful efficacy, with 64.7% of patients achieving ≥50% PSA reductions and 39.2% achieving ≥90% PSA reductions. Among taxane-naïve patients, PSA reductions were even more pronounced, with 75.0% achieving ≥50% declines and 53.6% achieving ≥90% declines. In a subset of taxane-naïve patients with bone-only disease, confirmed ≥50% PSA reductions reached 88.2%, and ≥90% reductions reached 76.5%, underscoring robust antitumor activity in a difficult-to-treat population.
Patients received docetaxel every three weeks and pasritamig every six weeks, with some continuing pasritamig beyond chemotherapy discontinuation. The ability to maintain treatment beyond docetaxel supports the potential for sustained immune-mediated disease control. These early findings provide a compelling rationale for the ongoing Phase 3 studies evaluating pasritamig both as monotherapy and in combination with docetaxel in the mCRPC setting.
Favorable Safety Profile Without Cytokine Release Syndrome
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Importantly, the combination demonstrated a safety profile consistent with docetaxel alone, with no new or unexpected safety signals observed. The most common treatment-related adverse events included fatigue, alopecia, diarrhea, nausea, peripheral edema, and neuropathy—events consistent with established chemotherapy effects. Notably, Grade 3 or higher adverse events were attributed to docetaxel in 29.4% of patients, compared with only 2% attributed to pasritamig, indicating limited additional toxicity from the investigational agent. Crucially, no patients experienced cytokine release syndrome of any grade, and no treatment-related deaths were reported, reinforcing the tolerability of this T-cell engaging approach in an outpatient setting.
Novel KLK2-Targeted T-Cell Engagement Strategy
Pasritamig is an investigational bispecific antibody targeting CD3 on T cells and human kallikrein 2 (KLK2), a prostate-specific antigen with minimal expression outside prostate tissue. By binding both CD3 and KLK2, the therapy is designed to redirect and activate T cells directly against prostate cancer cells, providing focused immune engagement while potentially minimizing off-target effects. This mechanism represents a differentiated strategy within immuno-oncology, particularly in mCRPC, where immune checkpoint inhibitors alone have demonstrated limited activity.
Metastatic castration-resistant prostate cancer remains a highly aggressive disease with median overall survival often ranging between 15 and 36 months, depending on disease burden and prior therapies. With limited durable treatment options available, innovative immunotherapy combinations are urgently needed. Pasritamig has already received Fast Track designation from the U.S. Food and Drug Administration and Breakthrough Therapy Designation in China, signaling regulatory recognition of its clinical potential.
As Johnson & Johnson advances the KLK2-comPAS and KLK2-PASenger Phase 3 trials, the combination of pasritamig and docetaxel could redefine treatment paradigms in advanced prostate cancer by integrating next-generation T-cell engagement with established chemotherapy backbones. If confirmed in larger studies, this approach may represent a meaningful step forward in expanding immunotherapy’s role in mCRPC.
Source: Johnson & Johnson press release
