A phase I first in human, open-label, multicenter study of BI3706674, KRAS multi-inhibitor, monotherapy in patients with advanced solid tumors bearing KRAS WT amp.

作者：Andreas Varkaris, Yasutoshi Kuboki, Steven B. Maron, Shigehisa Kitano, Keun-Wook Lee, Min-Hee Ryu, Tanios S. Bekaii-Saab, Yuki Fukuyama, J. Villa-Uribe, Shorena Archuadze, Kohei Shitara · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.2_suppl.380 · 被引用次数：3 · 研究领域：Protein Kinase Regulation and GTPase Signaling、HER2/EGFR in Cancer Research、Colorectal Cancer Treatments and Studies

380 Background: KRAS amplifications (amp) occur in ~2% of solid tumors, representing a high unmet need for effective targeted therapies. BI3706674 binds to GDP-bound KRAS and locks KRAS protein in an inactive form. In preclinical models, BI3706674 has shown potent inhibition of KRAS-amp tumors. Methods: This is a Phase Ia/b trial (NCT06056024) to explore the safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of BI 3706674 in patients (pts) with unresectable or metastatic KRAS wild type amp or KRAS G12V mutated (mut) solid tumors. The trial aimed to define the maximum tolerated dose (MTD). Pts (ECOG 0 -1) received BI 3706674 daily per os at 50 - 1200 mg doses. Dose escalation (DE) was guided by a Bayesian logistic regression model. This report focuses on KRAS wt amp pts from Phase Ia (DE). Results: As of 31 July 2025, 46 pts had received BI 3706674. Pts (n=15/46) with KRAS wt amp tumors had upper gastrointestinal tract (uGI) cancer [n=9: gastric (GAC;n=5), oesophageal (EAC; n=2), gastroesophageal junction (GEJC; n=2) cancers], Cholangiocarcinoma (n=1), colorectal (CRC; n=4), and ovarian (OC; n=1) cancers. Pts were treated at 200 mg (n=2), 400 mg (n=1), 800 mg (n=5), 1200 mg (n=7) doses; males: n=11; ECOG 1: n=10; median age - 62 years (range 38–83); median number of prior treatment lines was 3 (range 1-6). AEs were reported in 15 pts (100%), including 12 pts (80%) with treatment-related AEs (TRAE). High-grade AEs (Grade 3-5) were reported in 10 pts (66.7%), incl...