Johnson & Johnson's Pasritamig Shows Promising Anti-Tumor Activity in First-in-Human Prostate Cancer Trial
核心洞察
Johnson & Johnson announced first-in-human Phase 1 results for pasritamig (搜索), a novel bispecific T-cell engager targeting KLK2 (搜索), showing promising anti-tumor activity in metastatic castration-resistant prostate cancer (搜索) patients.
The study demonstrated a favorable safety profile with 40% of patients experiencing no treatment-related adverse events and no treatment discontinuations due to toxicity.
Among 33 patients in the efficacy group, 42.4% achieved ≥50% PSA reduction with a median radiographic progression-free survival of 7.9 months.
Johnson & Johnson announced promising first-in-human results for pasritamig (搜索) (JNJ-78278343), a novel bispecific T-cell-engaging antibody that demonstrated early anti-tumor activity in patients with metastatic castration-resistant prostate cancer (搜索) (mCRPC). The Phase 1 study data, presented at the 2025 American Society of Clinical Oncology Annual Meeting and published simultaneously in The Journal of Clinical Oncology, represent a significant milestone for this first-in-class therapeutic approach targeting human kallikrein 2 (搜索) (KLK2 (搜索)).
Novel Mechanism Targets Prostate-Specific Antigen
Pasritamig (搜索) represents a differentiated approach to T-cell engagement, designed to bind both CD3 (搜索) on T-cells and KLK2 (搜索), a prostate-specific antigen with minimal expression outside the prostate. The drug activates T-cells by binding to CD3 and directing them to KLK2-expressing tumor cells, engaging the body's immune system to specifically target cancerous cells while potentially reducing the high-grade toxicities historically associated with T-cell engagers.
"These first-in-human results for pasritamig (搜索) are highly encouraging, demonstrating that KLK2 (搜索) is a viable target for T-cell engagers in metastatic castration-resistant prostate cancer (搜索)," said Capucine Baldini, M.D., Ph.D., from the Drug Development Department at Institut Gustave Roussy and presenting author.
Phase 1 Study Design and Patient Population
The Phase 1 first-in-human study (NCT04898634) evaluated 174 patients with ages ranging from 36 to 89 years old who had received an average of four prior therapies (range 1-13). The recommended phase 2 dose (RP2D) was established as 3.5mg on day 1, 18mg on day 8, 300mg intravenously on day 15, and then once every six weeks.
Within the RP2D safety group (n=45), all patients had previously received androgen receptor pathway inhibitors, 75.6% had undergone taxane chemotherapy, and 37.8% had been treated with Lutetium 177 vipivotide tetraxetan prostate-specific membrane antigen radioligand therapy.
Favorable Safety Profile Enables Outpatient Administration
The safety data revealed a manageable toxicity profile that supports community-based treatment delivery. The most common treatment-related adverse events (TRAEs) were Grade 1/2 infusion-related reactions (24.4%), Grade 1 cytokine release syndrome presenting as fever only (8.9%), with no steroid or tocilizumab administration required. Notably, 40% of patients experienced no treatment-related adverse events at all.
No TRAEs leading to treatment discontinuation or dose reduction were reported, and no immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. Grade 3 TRAEs were infrequent, occurring in 4.4% of patients with transient AST/ALT increases and neutropenia. No dose-limiting toxicities were reported.
Efficacy Results Show Durable Disease Control
Among the 33 patients in the RP2D efficacy group treated once every six weeks, 42.4% achieved a 50% or greater reduction in their prostate-specific antigen (PSA) levels. The median radiographic progression-free survival (rPFS) was 7.9 months (95% confidence interval 2.9, not estimable), with 21.2% of patients continuing therapy. Treatment with pasritamig (搜索) showed durable disease control and rPFS that compares favorably to historical data in heavily pretreated patients with mCRPC.
Addressing Critical Unmet Medical Need
Metastatic castration-resistant prostate cancer (搜索) represents a challenging clinical scenario where the disease progresses despite androgen deprivation therapy. Overall survival from diagnosis of mCRPC patients ranges from 13.5 to 31.6 months, and is lower in patients who have progressed on therapy. Treatment options remain limited, underscoring the urgent need for safer and more effective therapies.
"Metastatic castration-resistant prostate cancer (搜索) remains one of the most difficult stages of prostate cancer (搜索) to treat, particularly for patients who haven't responded well to previous treatments," said Jeff Infante, M.D., Vice President of Early Clinical Development and Translational Research at Johnson & Johnson Innovative Medicine. "This investigational approach underscores our commitment to developing innovative and practice-changing medicines that are well-tolerated and can be easily administered in community practice settings."
The favorable safety profile of the RP2D regimen enabled convenient outpatient administration on a patient-friendly, once-every-six-weeks schedule, potentially improving treatment accessibility and patient quality of life compared to more intensive dosing regimens typically required for T-cell engagers.