Phase 1/2 study of YL201, an anti-B7H3 antibody–drug conjugate (ADC), in patients with relapsed or refractory (R/R) Ewing sarcoma and chondrosarcoma.

Abstract

11510 Background: The prognosis for R/R sarcoma remains dismal with limited effective treatment options. YL201 is a B7H3-targeting ADC with promising activity in multiple advanced solid tumors. Here, we report the safety and preliminary efficacy of YL201 monotherapy in patients with Ewing sarcoma (EWS) and chondrosarcoma (CHS) from a phase 1/2 study. Methods: Patients with histologically confirmed sarcoma who had an ECOG PS of 0 or 1 and progressed on ≥1 prior line of systemic therapies were enrolled and treated with YL201 intravenously Q3W at 2.0 mg/kg or 2.4 mg/kg until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: Thirty-two patients with sarcoma were enrolled, including EWS (n=20), CHS (n=10), osteosarcoma (n=1), and soft tissue sarcoma (n=1). The overall population had a median age of 34.0 years (range: 19–69), with 81.3% male and 46.9% having an ECOG PS of 1. Patients had a median of 1 prior line of therapy (range: 1–6), with 96.9% having received prior chemotherapy and 37.5% having received targeted therapy. As of December 12, 2025, the median follow-up was 11.4 months (95% CI: 9.1–13.2). In EWS sub-cohort, the confirmed ORR was 50.0% (95% CI: 27.2–72.8) with a median DoR of 6.5 months (95% CI: 2.8–NR), and DCR was 95.0% (95% CI: 75.1–99.9). Median PFS was 5.5 months (95% CI: 2.8–7.9), while OS data remained immature. In CHS sub-cohort, antitumor activity was observed with a confirmed ORR of 10.0% (95% CI: 0.3–44.5) and a DCR of 90.0% (95% CI: 55.5–99.7). The median PFS was 11.7 months (95% CI: 3.9–NR), and median OS was not reached. Membrane B7H3 expression was detected by immunohistochemistry in 42.1% of EWS and 44.4% of CHS patients, whereas the remainder exhibited no membrane B7H3 expression. However, no association was observed between tumor response and B7H3 expression level in either sub-cohort. Among all 32 patients enrolled, the treatment-related adverse events (TRAEs) of any grade and grade ≥3 occurred in 100.0% and 34.4% of patients, respectively. The most common grade ≥3 TRAEs included lymphopenia (15.6%), neutropenia (9.4%), thrombocytopenia (9.4%), leukopenia (6.3%), and anemia (6.3%). No interstitial lung disease or pneumonitis was observed. The rate of treatment discontinuation due to TRAEs was low at 3.1%, and no treatment-related deaths were reported. Conclusions: YL201 showed promising antitumor activity and manageable safety profile in patients with R/R EWS and CHS, with a particularly encouraging ORR in EWS. Given the high incidence of Ewing sarcoma in adolescents, these findings support further evaluation of YL201 in pediatric populations. Clinical trial information: NCT06057922 .