Efficacy and safety of olomorasib, a second-generation KRAS G12C inhibitor, plus cetuximab in KRAS G12C-mutant advanced colorectal cancer.

作者：Antoine Hollebecque, Takafumi Koyama, Yutaka Fujiwara, Yonina R. Murciano‐Goroff, Philippe A. Cassier, Natraj Reddy Ammakkanavar, Dustin A. Deming, Carlos Gomez‐Roca, Sae‐Won Han, Mohamedtaki Abdulaziz Tejani, Anthony B. El-Khoueiry, Nagla Fawzy Abdel Karim, Samantha Bowyer, Victor T. G. Lin, Samuel McNeely, Xintian You, Aaron Chen, Aaron Alan Fink, Melinda D. Willard, Yasutoshi Kuboki · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.3507 · 被引用次数：8 · 研究领域：Protein Kinase Regulation and GTPase Signaling、Colorectal Cancer Treatments and Studies、PI3K/AKT/mTOR signaling in cancer

3507 Background: Olomorasib, a potent and selective second-generation KRAS G12C inhibitor (G12Ci), has demonstrated promising efficacy and a favorable safety profile in KRAS G12C-mutant cancers. Based on emerging nonclinical and clinical data, combining a KRAS G12Ci with cetuximab offers a compelling opportunity to improve outcomes in patients (pts) with KRAS G12C-mutant colorectal cancer (CRC). Here we report updated results from a phase 1/2 study (NCT04956640) on the safety, tolerability and optimal dose of olomorasib + cetuximab in pts with KRAS G12C-mutant CRC. Methods: Pts with advanced KRAS G12C-mutant CRC (tissue or plasma) previously treated with ≥1 prior oxaliplatin- or irinotecan-containing regimen were eligible and enrolled into dose escalation/expansion or optimization at 2 doses of olomorasib (100 and 150 mg, orally BID). Dose escalation of olomorasib + cetuximab followed a mTPI-2 method. Key objectives were safety and to determine the optimal dose of olomorasib + cetuximab. Antitumor activity per RECIST v1.1 was studied in pts with ≥1 post-baseline response assessment or who discontinued before a first response assessment. Results: As of 13 November 2024, 93 pts received olomorasib + cetuximab in dose escalation/expansion (n=49) or optimization (n=44). Median age was 58 yrs (range, 35-82) and median number of prior therapies was 3 (range, 1-8). All grade TRAEs in ≥20% of pts were dermatitis acneiform (58%), diarrhea (38%), dry skin (31%), paronychia (28%), hypom...