KROCUS: A phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC.

作者：Vanesa Gregorc, María González‐Cao, Stefania Salvagni, Anna Koumarianou, Ignacio Gil‐Bazo, Michele Maio, Santiago Viteri, Margarita Majem, Vanesa Gutiérrez, Reyes Bernabé, Miguel F. Sanmamed, Huaqiang Zhu, Haige Shen, Yu Wang, Rafael Rosell · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.17_suppl.lba8511 · 被引用次数：26 · 研究领域：Cancer Treatment and Pharmacology、Colorectal Cancer Treatments and Studies、HER2/EGFR in Cancer Research

LBA8511 Background: Fulzerasib (GFH925), a KRAS G12C inhibitor, showed substantial efficacy in previously treated NSCLC patients (pts) as monotherapy. Activation of epidermal growth factor receptor (EGFR) is identified to be one of the dominant mechanisms for KRAS inhibition resistance. Preclinical evidence showed synergistic activity in KRAS G12C mutant NSCLC modeling using fulzerasib in combination with cetuximab. Here we report the first results for a KRAS G12C inhibitor combined with an anti-EGFR antibody in NSCLC pts as front-line treatment. Methods: KROCUS (NCT05756153) was an open-label, single-arm, multi-center, Phase II study with the primary objective to evaluate the efficacy of fulzerasib in combination with cetuximab in pts with previously untreated advanced NSCLC harboring KRAS G12C mutation. Secondary objectives included safety/tolerability, pharmacokinetics and biomarkers. Pts were enrolled to receive fulzerasib (oral, 600 mg BID) and cetuximab (intravenous, 500 mg/m 2 , every two weeks [Q2W]) combination treatment in a 28-day cycle. Results: As of Jan. 30, 2024, a total of 27 pts (median age: 68 yrs old; 55.6% female) were treated, 11 (40.7%) with baseline brain metastases. Of 20 pts who had at least one post-treatment tumor assessment, ORR was 80.0% (95% CI: 56.3, 94.3, including one CR), of whom eight pts had ≥ 50% tumor shrinkages in the target lesions. Disease control rate (DCR) was 100% (95% CI: 83.2, 100.0). Five out of seven pts (71.4%) with brain metas...