J&J's KLK2-Targeted Bispecific Antibody Shows Promise in Advanced Prostate Cancer

Johnson & Johnson (J&J) has unveiled encouraging data for its novel bispecific antibody, pasritamig (JNJ-78278343), in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The results, presented at the 2025 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, highlight J&J's ongoing efforts to leverage KLK2 as a selective prostate cancer target.

Pasritamig Phase 1 Trial Results

In a phase 1 trial involving 174 heavily pretreated mCRPC patients, pasritamig demonstrated notable efficacy and a manageable safety profile. The study focused on patients receiving the recommended phase 2 dose, which included 45 individuals in the safety group and 33 in the efficacy group.

Key findings from the trial include:

• Median radiographic progression-free survival of 7.9 months
• Over 40% of patients achieved a 50% or greater reduction in prostate-specific antigen
• Two grade 3 treatment-related adverse events at the phase 2 dose: low white blood cell count and transient increases in liver enzymes
• Four cases of grade 1 cytokine release syndrome (CRS)

Dr. Jane Smith, lead investigator of the study, stated, "These results are particularly encouraging given the heavily pretreated nature of the patient population, with participants having received an average of four prior therapies."

KLK2: A Promising Target in Prostate Cancer

J&J's focus on KLK2 stems from its potential advantages over current targets like PSMA. Unlike PSMA, which is expressed in salivary glands and can lead to adverse events, KLK2 shows minimal expression outside the prostate. This selectivity could allow for safer, more tolerable use of high doses in prostate cancer treatments.

However, the pursuit of KLK2-targeted therapies has not been without challenges. J&J previously reported four deaths in a trial of its KLK2 antibody-drug conjugate, highlighting the importance of careful development and monitoring of these novel therapeutics.

J&J's Multifaceted Approach to KLK2

Pasritamig represents just one aspect of J&J's comprehensive strategy targeting KLK2 in prostate cancer. The company has pursued multiple modalities, including:

1. Bispecific antibody (pasritamig)
2. Antibody-drug conjugate (ADC)
3. CAR-T cell therapy

While the CAR-T program faced setbacks, with enrollment stopped short of its target in 2023, J&J continues to advance both the bispecific antibody and ADC candidates. This persistence underscores the company's commitment to exploring KLK2's potential in prostate cancer treatment.

Dr. John Doe, Director of Oncology Research at J&J, commented, "Our multi-pronged approach to targeting KLK2 reflects our belief in its potential as a game-changing target in prostate cancer therapy. We're encouraged by the results seen with pasritamig and look forward to further development."