Phase 2 study of YL201, an anti-B7H3 antibody–drug conjugate (ADC), in heavily pretreated metastatic castration-resistant prostate cancer (mCRPC).

Abstract

5015 Background: The treatment of mCRPC remains challenging, especially for patients who progressed on androgen receptor axis-targeted therapy (ARAT) with or without taxane-based chemotherapy. YL201 is a B7H3-targeting ADC with promising activity in advanced solid tumors. Here, we report the safety and preliminary efficacy of YL201 monotherapy in heavily pretreated mCRPC patients from a phase 2 study. Methods: Patients with mCRPC who had an ECOG PS of 0 or 1 and progressed on ≥1 prior line of ARAT and ≤2 lines of chemotherapy were enrolled and treated with YL201 intravenously Q3W at 2.0 or 2.4 mg/kg until disease progression or unacceptable toxicity. Primary endpoints were objective response rate (ORR) and radiographic progression-free survival (rPFS) per RECIST v1.1 and PCWG3 criteria. Secondary endpoints included PSA 50 response rate, duration of response (DoR), overall survival (OS), and safety. Results: As of 12 December 2025, 82 patients were enrolled (34 at 2.0 mg/kg; 48 at 2.4 mg/kg) with a median follow-up of 12.2 months (95% CI: 11.2–13.4). The median age was 67.0 years, 65.9% had an ECOG PS of 1, and 43.9% had visceral metastases (22.0% with liver metastasis) at study entry. Patients had a median of 4 prior line of therapy (range: 1–8), with 100% having received ARAT and 70.7% having received taxane-based chemotherapy. Across both dose levels, confirmed PSA 50 response rate was 38.5% (95% CI: 27.7–50.2), with a median duration of PSA response of 13.6 months (95% CI: 6.9–NR). Confirmed ORR was 29.5% (95% CI: 18.5–42.6), with a median DoR of 9.9 months (95% CI: 6.5–NR). Median rPFS was 9.1 months (95% CI: 7.4–12.0), while median OS remained immature. Higher PSA 50 response rate, ORR and rPFS were observed at 2.4 mg/kg compared with 2.0 mg/kg (48.9% vs . 24.2%, 33.3% vs . 24.0%, 11.8 vs . 9.0 months, respectively). Notably, in patients with baseline visceral metastases, YL201 still showed encouraging efficacy with a confirmed PSA 50 response rate of 54.5%, confirmed ORR of 28.6%, and median rPFS of 11.8 months at 2.4 mg/kg. Membrane B7H3 expression was detected in most tumor samples (median H-score: 185; range: 0–290), with no association observed between response and B7H3 expression level. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 43.9% of patients. The most common grade ≥3 TRAEs included neutropenia (29.3%), anemia (22.0%), leukopenia (18.3%), and thrombocytopenia (9.8%). No interstitial lung disease or pneumonitis was observed. The rate of treatment discontinuation due to TRAEs was 1.2%, and no treatment-related deaths were reported. Conclusions: YL201 showed promising antitumor activity and manageable safety profile in heavily pretreated mCRPC patients. These findings support further development of YL201 in mCRPC, especially for those who progressed after ARAT with or without taxane-based chemotherapy, and those with visceral metastases. Clinical trial information: NCT06241846 .