BI 905711, a TRAILR2/CDH17 Bispecific Antibody, Alone or with Chemotherapy for Patients with Advanced Gastrointestinal Cancers: Phase I Study Findings

作者：James J. Harding, Ralf Hofheinz, Elena Élez, Yasutoshi Kuboki, Drew Rasco, Michael Cecchini, Lin Shen, Min He, Shorena Archuadze, Niraj Chhaya, Franziska Haderk, Lisa Mészáros, Stefan Wölke, Tetsuya Katakabe, Robert M. Lorence, Eric Van Cutsem, Scott Kopetz, Shubham Pant · 发表于：Cancer Research Communications · 年份：2026 · DOI：10.1158/2767-9764.crc-25-0638 · 被引用次数：2 · 研究领域：Colorectal Cancer Treatments and Studies、Cancer Immunotherapy and Biomarkers、HER2/EGFR in Cancer Research

PURPOSE: BI 905711, a TRAILR2/cadherin-17 (CDH17) bispecific antibody, demonstrated preclinical apoptotic pathway activation and antitumor activity. Two phase Ia/Ib studies tested BI 905711 monotherapy (NCT04137289) or combination therapy (NCT05087992) in advanced, refractory gastrointestinal (GI) cancers. PATIENTS AND METHODS: Both studies aimed to determine the maximum tolerated dose (MTD; phase Ia) and recommended phase II dose (RP2D)/recommended dose for expansion (RDE; phase Ib). In phase Ia, patients received BI 905711 monotherapy (0.02-4.8 mg/kg) or 0.6 to 1.2 mg/kg plus biweekly folinic acid (leucovorin), 5-fluorouracil, and irinotecan (FOLFIRI) and bevacizumab. Phase Ib assessed selected doses and regimens given biweekly or weekly (3 weeks on and 1 week off). Safety, efficacy, and pharmacokinetics/pharmacodynamics were evaluated. RESULTS: In NCT04137289, 110 patients [median age 61 years; 80% with colorectal cancer; median of three prior therapies (range, 1-6)] received monotherapy. No dose-limiting toxicities (DLT) occurred, MTD was not reached, RP2D was not determined, and 48.2% of patients had treatment-related adverse events (TRAE), most commonly nausea (16.4%). In 104 response-evaluable patients, 22.1% achieved stable disease (SD). In NCT05087992, 12 patients with colorectal cancer (median age 54.5 years) received combination treatment. Two patients reported DLTs, MTD was not reached, and the selected RDE was 0.6 mg/kg plus biweekly FOLFIRI and bevacizumab. Most...