Single-Agent Divarasib in Patients With KRAS G12C-Positive Non-Small Cell Lung Cancer: Long-Term Follow-Up of a Phase I Study
- Author(s)
- Sacher, AG; Miller, WH, Jr; Patel, MR; Paz-Ares, L; Santoro, A; Ahn, MJ; Dziadziuszko, R; Freres, P; Luo, J; Bowyer, S; Desai, J; Markman, B; de Miguel, M; Deva, S; Falcon, A; Alonso, G; Guedes, JD; Kim, SH; Krebs, MG; Laurie, SA; Massarelli, E; Medina, L; Prenen, H; Amatu, A; Van Dongen, M; Choi, Y; Hou, X; Qi, T; Lin, MT; Koli, K; Mayo, MC; Yau, KK; Royer-Joo, S; Chang, J; Jun, T; Dharia, NV; Schutzman, JL; LoRusso, P; GO42144 Investigator Study Group;
- Journal Title
- Journal of Clinical Oncology
- Publication Type
- Online publication before print
- Abstract
- Divarasib (GDC-6036), an oral, highly potent and selective next-generation KRAS G12C inhibitor, has demonstrated a manageable safety profile and promising antitumor activity in patients with advanced KRAS G12C-positive non-small cell lung cancer (NSCLC). Here, we report long-term (≥1 year) follow-up of single-agent divarasib from the ongoing, open-label, and multicenter phase I study (ClinicalTrials.gov identifier: NCT04449874). The primary objective was safety, and the other objectives included preliminary antitumor activity. Overall, 65 patients with advanced KRAS G12C-positive NSCLC received single-agent oral divarasib 50-400 mg once daily and 31 patients (48%) were treated beyond 1 year. Divarasib continued to be well tolerated, and the safety profile beyond 1 year was consistent with the overall safety profile. In patients with measurable disease at baseline across all dose levels (n = 63), the confirmed objective response rate was 55.6% (95% CI, 42.5 to 68.1), and the median duration of response was 18.0 months (95% CI, 11.1 to 24.9). The median progression-free survival was 13.8 months (95% CI, 9.8 to 25.4) in the overall population (N = 65) and 15.3 months (95% CI, 12.3 to 26.1) among patients assigned to the 400-mg dose level (n = 44). With extended follow-up, divarasib demonstrated long-term safety and antitumor activity in patients with advanced KRAS G12C-positive NSCLC.
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1200/jco-25-00040
- Open Access at Publisher's Site
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Creation Date: 2025-08-08 07:40:15
Last Modified: 2025-08-08 07:42:02