Phase 1/2 study of YL201, an anti-B7H3 antibody–drug conjugate (ADC), in patients with previously treated advanced pancreatic ductal adenocarcinoma (PDAC).

Abstract

4208 Background: The prognosis for patients with advanced PDAC after failure of first-line therapy remains dismal with limited effective treatment options. There is a critical unmet need for novel therapeutic agents in the second-line and beyond (2L+) setting. YL201 is a B7H3-targeting ADC with promising clinical activity in multiple advanced solid tumors. Here, we report the safety and preliminary efficacy of YL201 monotherapy in patients with 2L+ PDAC from a phase 1/2 dose expansion study. Methods: Patients with metastatic PDAC who had progressed on at least one prior line of systemic therapies without irinotecan 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: A total of 60 patients were enrolled, including 30 treated at 2.0 mg/kg and 30 at 2.4 mg/kg. The median age was 61.0 years, 63.3% were male, and 91.7% had an ECOG PS of 1. 48.3% of patients had ≥3 metastatic sites at baseline. Patients had received a median of 1 prior line of therapy (range: 1–3). 90.0% had received prior gemcitabine-based regimen and 46.7% had received prior fluoropyrimidine. As of 12 December 2025, the median follow-up was 9.2 months (95% CI: 8.2–9.8). Among the 60 patients enrolled, the confirmed ORR was 28.3% (95% CI: 17.5–41.4) with a median DoR of 7.6 months (95% CI: 4.9–NR), and the DCR was 85.0% (95% CI: 73.4–92.9). The median PFS was 7.7 months (95% CI: 5.5–9.7), and the median OS was 14.6 months (95% CI: 8.2–NR). Membrane B7H3 expression was detected by immunohistochemistry in most tumor samples with a median H-score of 65 (range: 0–275). However, no association was observed between tumor response and B7H3 expression level in PDAC patients. Treatment-related adverse events (TRAEs) of any grade and grade ≥3 occurred in 100.0% and 43.3% of patients, respectively. The most common grade ≥3 TRAEs included leukopenia (16.7%), neutropenia (15.0%), anemia (15.0%), and hypokalemia (6.7%). The rate of treatment discontinuation due to TRAEs was 5.0%, and no treatment-related deaths were reported. Conclusions: YL201 monotherapy showed promising antitumor activity and a manageable safety profile in pretreated patients with advanced PDAC. These compelling results warrant further investigation of YL201 in a randomized controlled trial for patients with advanced PDAC in the 2L+ setting. Clinical trial information: NCT06057922 .