B7-H3 ADC YL201 Delivers Encouraging Results in Advanced mCRPC

YL201, a B7-H3–targeting antibody–drug conjugate, is showing notable activity in advanced metastatic castration-resistant prostate cancer (mCRPC), including patients who have progressed after androgen receptor–targeted therapy and chemotherapy. In a phase 2 study of 82 heavily pretreated patients, the drug delivered a confirmed PSA50 response rate of 38.5%, an objective response rate of 29.5%, and a median radiographic progression-free survival of 9.1 months.

This was a clinically difficult population, with a median of four prior treatment lines and more than 70% previously exposed to taxane-based chemotherapy. Nearly half of the patients had visceral metastases, including a substantial proportion with liver involvement, a subgroup typically associated with poor outcomes and resistance to conventional therapies.

Efficacy was stronger at the 2.4 mg/kg dose, where PSA responses approached 49% and rPFS extended to 11.8 months. Importantly, activity was maintained in patients with visceral metastases, a subgroup typically associated with poor outcomes, with PSA responses exceeding 50% and similar progression-free survival.

Safety was manageable and primarily hematologic, with grade 3 or higher adverse events in 43.9% of patients, most commonly neutropenia and anemia. Discontinuation due to toxicity was rare, and no treatment-related deaths or interstitial lung disease were reported.

Overall, YL201 demonstrates clinically meaningful activity in a difficult-to-treat population and warrants further development, particularly as a potential option for patients with visceral disease or those ineligible for PSMA-targeted therapies.

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