YL201 (B7-H3–targeted ADC) posts 33% ORR and 11.8-mo rPFS in heavily pretreated mCRPC (2.4 mg/kg)

YL201 is an anti-B7H3 antibody–drug conjugate (ADC) evaluated as monotherapy in a Phase 2 study in metastatic castration-resistant prostate cancer after ≥1 androgen receptor axis-targeted therapy (ARAT) and ≤2 chemotherapy lines (NCT06241846); 82 patients were treated Q3W at 2.0 mg/kg (n=34) or 2.4 mg/kg (n=48), with high-risk features including visceral metastases in 43.9% (liver 22.0%) and a median 4 prior therapy lines. Across doses, confirmed PSA50 response was 38.5% and confirmed ORR was 29.5% with median DoR 9.9 months and median rPFS 9.1 months; activity numerically favored 2.4 mg/kg (PSA50 48.9%, ORR 33.3%, rPFS 11.8 months), including in visceral disease at 2.4 mg/kg (PSA50 54.5%, ORR 28.6%, rPFS 11.8 months). Safety was primarily myelosuppression (grade ≥3 TRAEs 43.9%: neutropenia 29.3%, anemia 22.0%, leukopenia 18.3%, thrombocytopenia 9.8%); discontinuation for TRAEs was 1.2% and no ILD/pneumonitis was reported—an important differentiator vs some ADC classes, while efficacy benchmarks in this post-ARAT/post-taxane space include cabazitaxel rPFS ~8.0 months (CARD) and ^177Lu-PSMA-617 + SOC rPFS 8.7 months with ORR 29.8% in PSMA-selected patients (VISION), making YL201’s 2.4 mg/kg rPFS/ORR look at least “in-family” despite cross-trial differences.