Single-Agent Divarasib in Patients With <i>KRAS G12C</i> –Positive Non–Small Cell Lung Cancer: Long-Term Follow-Up of a Phase I Study
Adrian G. Sacher, Wilson H. Miller, Manish R. Patel, Luis Paz‐Ares, Armando Santoro, Myung‐Ju Ahn, Rafał Dziadziuszko, Pierre Frères, Jia Luo, Samantha Bowyer, Jayesh Desai, Ben Markman, Maria J. de Miguel, Sanjeev Deva, Alejandro Falcón, Guzmán Alonso, João Daniel Guedes, Se Hyun Kim, Matthew Krebs, Scott A. Laurie, Erminia Massarelli, Laura Medina, Hans Prenen, Alessio Amatu, Marloes van Dongen, Yoonha Choi, Xuefeng Hou, Ting Qi, Mark T. Lin, Kalpesh Koli, Mariah C. Mayo, Kenneth K. Yau, Stephanie Royer‐Joo, Julie Chang, Tomi Jun, Neekesh V. Dharia, Jennifer L. Schutzman, Patricia LoRusso, on behalf of the GO42144 Investigator Study group, Samantha Bowyer, Rasha Cosman, Jayesh Desai, Ben Markman, Pierre Frères, Marc Lambrechts, Hans Prenen, Carlos Barrios, J.D. Guedes, Sérgio de Azevedo, Rita de Cássia Costamilan, Carolina Gomes Jacobina Silva, Tabatha Nakakogue Dallagnol, Scott A. Laurie, Wilson H. Miller, Adrian G. Sacher, István Láng, István Takács, Ravit Geva, Ruth Perets, Einat Shacham‐Shmueli, Chiara Cremolini, Gianluca Del Conte, Angelo Delmonte, Armando Santoro, Salvatore Siena, Mansoor N. Saleh, Myung‐Ju Ahn, Sae‐Won Han, Tae Won Kim, Jong-Seok Lee, Hans Gelderblom, Eelke Gort, Loes M Latten-Jansen, Marloes Van Dongen, Sanjeev Deva, Rajiv Kumar, Øystein Fløtten, Tormod Kyrre Guren, Rafał Dziadziuszko, Jacek Mackiewicz, Rafał Stec, Р. С. Сафин, Á. Ruiz-Pérez, Maria de Miguel Luken, Alejandro Falcon, Elena Garralda Cabanas, Laura Medina, Víctor Moreno, Luis Paz-Ares Rodriguez, Christian Britschgi, Eugenio Fernández, Simon Häfliger, Sacha Rothschild, Martin Förster, Robert Jones, Matthew Krebs, Raid Aljumaily, Kathryn Arbor, Lyudmila Bazhenova, Timothy F. Burns
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.