FDA grants fast track designation to pasritamig for mCRPC

The FDA has granted fast track designation to pasritamig (JNJ-78278343), an investigational first-in-class bispecific T-cell-engaging antibody targeting human kallikrein 2 (KLK2) for patients with metastatic castration-resistant prostate cancer (mCRPC), Johnson & Johnson announced in a news release.¹

Fast track designation is awarded to novel agents that are intended to treat or prevent serious conditions and have the potential to address an unmet medical need. With this designation, the development process for pasritamig can benefit from more frequent engagement with the FDA as well as eligibility for accelerated approval and priority review.

Data from a phase 1 study (NCT04898634) of pasritamig were presented at the 2025 American Society of Clinical Oncology Annual Meeting, showing that the agent was well-tolerated and had encouraging preliminary anti-tumor activity in patients with mCRPC.^2,3 The study included 174 patients who had received at least 1 dose of pasritamig, with a median age of 69 years.

Safety data showed that 82.2% of patients reported at least 1 treatment-related adverse event (TRAE), which were generally low-grade. In total, 9.2% of patients experienced a grade 3 or higher TRAE.

The recommended phase 2 dose (RP2D) was chosen to be SUI 3.5 mg D1, SU2 18 mg D8, TD 300 mg D15, and 300 mg Q6W, all given as intravenous doses. In the patients that received this dosing schedule, the most common TRAEs were infusion-related reactions (22.2%), fatigue (15.6%), and cytokine release syndrome (CRS) (8.9%).

Further, in the RP2D population, the median radiographic progression-free survival was 7.9 months (95% CI, 2.9 to NE) at the time of data report. Data also showed that 42.4% of patients achieved a 50% or greater reduction in PSA levels.

“Pasritamig was very well tolerated (<10% of pts experienced CRS [all Gr1] at the RP2D) with promising antitumor activity, demonstrating proof of concept for KLK2 as a target amenable to T-cell redirection,” the authors concluded. “These results address an unmet need for a targeted T-cell based therapy that is safe to administer in an outpatient setting with clinically meaningful benefit in mCRPC.”

Additional data on pasritamig were also recently presented at the 2025 European Society for Medical Oncology Congress in Berlin, Germany, by Karen Autio, MD. Autio began the discussion by noting that previous data from the first-in-human study (NCT04898634) found that, compared with a Q3W dose schedule, weekly dosing of paritamig was associated with rising PSA values in a subset of patients.

The study also found that 300 mg IV Q6W dosing “optimized drug concentrations for efficacy and mitigates T-cell exhaustion.” Specifically, more patients who received the Q6W dosing interval achieved a complete response at any time compared with those who received the 300 mg IV Q3W schedule (44% vs 33%).

Autio explained, “This piqued our interest to understand the immunologic impact, alongside efficacy, of different dosing intervals and why Q6W was most optimal.”

Thus, a translation analysis was conducted to confirm the mechanism of action for pasritamig and the RP2D selection.

Overall, the authors reported, “Compared with QW or Q3W cohorts, pasritamig dosed at Q6W IV maintained a reprogrammable progenitor CD8 T cell population with lower expression of the apoptotic markers activated caspase-3 and γH2AX in PBMCs (n=186), suggestive of less AICD and less terminal T cell exhaustion and correlating with better clinical efficacy.”

Data also showed that a higher percentage of reprogrammable progenitor T cells was positively associated with a PSA response of 50% or higher, regardless of dose level.

These findings, they concluded, support the proposed mechanism of action of pasritamig as well as the RP2D.

DISCLOSURES: Autio noted financial, consulting, or advisory role disclosures with VIR Biotechnology, Amgen (Inst), AstraZeneca (Inst), Pfizer (Inst), Janssen (Inst), and Janux Therapeutics (Inst).

REFERENCES

1. Johnson & Johnson enters new era in solid tumors at ESMO 2025 with promising data across multiple cancer types. News release. Johnson & Johnson. October 15, 2025. Accessed October 21, 2025. https://innovativemedicine.jnj.com/us/news-center/oncology/johnson-johnson-enters-new-era-in-solid-tumors-at-esmo-2025-with-promising-data-across-multiple-cancer-types?sf229310720=1&sf229378866=1

2. Baldini C, Vinceneux A, Robbrecht DGJ, et al. Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer (mCRPC). Presented at: 2025 American Society for Clinical Oncology Annual Meeting. May 30-June 3, 2025. Chicago, Illinois. Abstract 5017

3. Johnson & Johnson unveils first-in-human results for pasritamig, showing early anti-tumor activity in prostate cancer. News release. Johnson & Johnson. June 1, 2025. Accessed October 23, 2025. https://www.jnj.com/media-center/press-releases/johnson-johnson-unveils-first-in-human-results-for-pasritamig-showing-early-anti-tumor-activity-in-prostate-cancer

4. Translational analyses of T cell phenotypes and their association with clinical efficacy in the first-in-human (FIH) trial of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer (mCRPC). Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract 2385MO