Safety and efficacy of D-1553 in KRAS G12C-mutated colorectal cancer: Results from a phase I/II study.

作者：Dan‐Yun Ruan, Myung Ah Lee, Yanhong Deng, Keun‐Wook Lee, Michael Millward, Jaspreet Singh Grewal, Shirish M. Gadgeel, Rachel E. Sanborn, Xinfang Hou, Shaozhong Wei, Seok Jae Huh, Furong Liu, Xiaoxi Xie, Ziyong Xiang, Zhe Shi, Yaolin Wang, Ling Zhang, Gary Richardson, Rui‐Hua Xu · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.16_suppl.3563 · 被引用次数：12 · 研究领域：Colorectal Cancer Treatments and Studies、Cancer Treatment and Pharmacology、Lung Cancer Treatments and Mutations

3563 Background: KRAS G12C mutation is an oncogenic driver that occurs in 3-4% of colorectal cancer (CRC). D-1553 is a novel oral and potent KRAS G12C inhibitor. This phase I/II open-label study (NCT04585035) is an international multicohort study evaluating the safety, tolerability, pharmacokinetics (PK) and efficacy of D-1553 in patients (pts) with KRAS G12C mutated locally advanced or metastatic solid tumors. The Phase I part was conducted to determine the recommended phase 2 dose (RP2D) of D-1553. The Phase II part enrolled multiple expansion cohorts of different cancer types. The endpoints of the study include clinical activity, safety and PK. Here we report preliminary data from pts with locally advanced unresectable or metastatic CRC receiving ≥ RP2D of D-1553 monotherapy. Methods: Pts with locally advanced unresectable or metastatic CRC with progression after standard treatment were enrolled in the Phase I and Phase II parts of the study. Pts were required to have KRAS G12C mutations in tumor or ctDNA samples and no prior KRAS G12C directed therapy. The current analysis includes CRC patients who were treated with D-1553 at RP2D (600 mg BID in Phase I and II) and above (800 mg BID in Phase I) as monotherapy. Results: As of 30 December 2022, 24 pts with previously heavily treated locally advanced or metastatic CRC (54.2% male; median age, 61.5 years [range 44, 74]; ECOG PS 0/1: 45.8%/54.2%) were enrolled and received D-1553 600 mg (n = 23) or 800 mg (n = 1) BID monothera...