Phase 1 safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of pasritamig in Asian population with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

172 Background: Pasritamig is a first-in-class bispecific antibody T-cell engager that simultaneously binds human kallikrein 2 (KLK2) on PC cells and CD3 receptor complexes on T cells. Tolerable safety profile and promising anti-tumor activity was reported for US & EU population. We report results for the Asian mCRPC population from a first-in-human study (NCT04898634) evaluating pasritamig in patients with advanced PC. Methods: The RP2D dose schedule of 3.5mg (step-up dose 1)-18mg (step-up dose 2)-300mg IV Q6W was administered. Pre-medication with dexamethasone (16 mg) was implemented for step-up and first treatment dose. The primary objective was safety. Secondary objectives included preliminary antitumor activity, PK and PD. Results: As of July 4, 2025, 22 Asian patients (17 Chinese, 5 Japanese, median [range] age 69 [52-85] years), with a median of 3 prior therapies (range 2-6; 100.0% ARPI, 95.5% taxane, 22.7% PARPi, 4.5% RLT), received at least 1 pasritamig dose. Fifteen patients had bone and/or lymph node metastasis only while the other 7 patients had visceral metastasis. No DLTs, pasritamig-related deaths or treatment discontinuations were reported. Sixteen (72.7%) patients reported ≥1 treatment-related AE (TRAE), and 8 (36.4%) patients experienced Grade ≥3 TRAE. Most (7/8) Grade ≥ 3 TRAEs were cytopenia (5 lymphopenia, 2 anemia), of which the majority (5/7) already had Grade 2 cytopenia at baseline. The other Grade 3 TRAE was dermatitis, which recovered in 22 days with steroid treatment. Two (9.1%) CRS cases were reported with the severity of Grade 1. No infusion-related reactions or ICANS were observed. The PSA50 response was 50.0% (10/20), including 4 responders with visceral metastases, and confirmed PSA50 was 35.0% (7/20) in the PSA-evaluable population. With a median follow up of 2.7 months, median rPFS was still not reached (95% CI: 1.81, NE) with 68.2% (15/22) patients ongoing. ORR in the patients with measurable disease was 11.1% (1/9), with response at a site of liver metastasis. PK was linear with a mean half-life of 14 days. Biomarker assessment revealed an elevated on-treatment IL-6 level in a patient who had Grade 1 CRS. Increases in on-treatment IFN-γ and CD38+/CD8+ T-cells were observed following pasritamig treatment, indicating peripheral T-cell activation consistent with the proposed MOA. A higher baseline frequency of PD-1+/CD8+ T-cells was noted in PSA50 responders. Conclusions: The safety, efficacy, PK and PD profile of pasritamig in Asia is broadly consistent with the US & EU population reported previously. Longer follow up for efficacy and further quantification of responses in visceral lesions are in progress. These results highlight the potential of pasritamig to fulfill the unmet need for a safe T-cell based therapy for mCRPC and support the inclusion of Asian patients in global phase 3 trials. Clinical trial information: NCT04898634 .