Johnson & Johnson has shared more data on its multifront attack on KLK2, linking a bispecific antibody to 7.9 months progression-free survival in hard-to-treat prostate cancer patients as it plans for further development.
J&J has identified KLK2 as the most selective prostate cancer marker. While PSMA is found in the salivary glands, leading to adverse events in recipients of medicines such as Novartis’ Pluvicto, KLK2 has minimal expression outside of the prostate and as such could support safe, tolerable use of high doses. However, safety was called into question when four recipients of J&J’s KLK2 radioligand therapy, died.
The latest results, which J&J shared at the 2025 American Society of Clinical Oncology (ASCO) annual meeting in Chicago this week, come from a phase 1 trial of another of the company’s KLK2 candidates. The bispecific pasritamig, also called JNJ-78278343, binds to CD3 and KLK2 to direct T cells to attack prostate cancer.
J&J tested pasritamig in 174 people with metastatic castration-resistant prostate cancer (mCRPC) who on average had received four prior therapies. The company focused its analysis on the people who received the recommended phase 2 dose, which included 45 patients in the safety group and 33 people in the efficacy group.
Everyone in the safety group had previously received androgen receptor pathway inhibitors. More than three-quarters of the patients had received taxane chemotherapy, and almost 38% had taken the PSMA radiopharmaceutical Pluvicto.
There were two grade 3 treatment-related adverse events—low white blood cells and transient increases in liver enzymes—at the phase 2 dose. Four people had cytokine release syndrome (CRS), but all cases were grade 1. CRS, including grade 2 cases, and grade 3 treatment-related adverse events were more common in the overall, 174-patient data set that included people who received higher doses.
At the phase 2 dose, more than two-fifths of patients had a 50% or greater reduction in prostate-specific antigen. Median radiographic progression-free survival was 7.9 months. More than one-fifth of the patients are continuing therapy. J&J said the disease control and survival data compare favorably to historical data in heavily pretreated mCRPC patients.
The authors of the ASCO abstract said phase 3 trials are planned. Advancing pasritamig quickly would cement J&J’s status as the front-runner in KLK2. Juri Biosciences licensed a KLK2xCD3 bispecific from EpimAb Biotherapeutics for up to $210 million last week, but J&J’s broad, sustained focus on the target stands out.
Pasritamig is one of three KLK2 candidates J&J has taken into the clinic. J&J began testing a KLK2 CAR-T candidate in humans in 2021 but stopped enrollment well short of its target in 2023. The CAR-T is not listed in J&J’s publicly disclosed pipeline. J&J continues to list the KLK2-directed radioligand therapy in its pipeline and to enroll patients in a phase 1 trial of the candidate.
The multifront attack is reminiscent of how the industry has gone after popular cancer targets such as BCMA and CLDN18.2. However, while those targets attracted a who’s who of drugmakers, J&J is by far the most active company in KLK2 and is almost single-handedly responsible for the multimodality push.