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
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (98)
Adrian G. Sacher
Wilson H. Miller
Department of Medicine, Division of Oncology, Jewish General Hospital, Montreal, QC, Canada
Manish R. Patel
Luis Paz-Ares
Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid
Jia Luo
Maria de Miguel
START Madrid CIOCC Hospital HM Sanchinarro, Madrid, Spain
Guzman Alonso
João Daniel Guedes
Hospital de Base de São José do Rio Preto, São José do Rio Preto, Brazil
Se Hyun Kim
Matthew G. Krebs
Scott A. Laurie
Ottawa Hospital Research Institute, Ottawa, ON, Canada
Alessio Amatu
Ting Qi
Kalpesh Koli
Genentech, Inc, South San Francisco, CA
Mariah C. Mayo
Genentech, Inc, South San Francisco, CA
Samantha Bowyer
Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia
Rasha Cosman
Jayesh Desai
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Ben Markman
Alfred Health and Monash University, Melbourne, VIC, Australia
Pierre Freres
University Hospital of Liege, Liege, Belgium
Marc Lambrechts
Hans Prenen
Carlos Barrios
Latin American Cooperative Oncology Group, Porto Alegre, Brazil
Joao Daniel Cardoso Guedes
Sérgio de Azevedo
Rita De Cassia Costamilan
Carolina Gomes Jacobina Silva
Tabatha Nakakogue Dallagnol
Scott Laurie
Wilson Miller
Adrian Sacher
István Láng
István Takács
Ravit Geva
Department of Radiation Oncology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
Ruth Perets
Rambam Medical Center and Technion-Israel Institute of Technology, Haifa, Israel
Einat Shacham-Shmueli
Institute of Oncology, Sheba Medical Center, Ramat Gan, Israel
Chiara Cremolini
Gianluca Del Conte
Angelo Delmonte
Armando Santoro
IRCCS Humanitas Research Hospital, Milan
Salvatore Siena
Mansoor Saleh
Myung-Ju Ahn
Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Sae-Won Han
Seoul National University Hospital and Seoul National University Cancer Research Institute, Seoul, Republic of Korea
Tae Won Kim
Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Jong-Seok Lee
Hans Gelderblom
Eelke Gort
Loes Latten-Jansen
Marloes Van Dongen
Netherlands Cancer Institute, Amsterdam, Netherlands
Sanjeev Deva
Department of Cancer Sciences, University of Auckland, Auckland, New Zealand
Rajiv Kumar
Øystein Fløtten
Tormod Guren
Rafal Dziadziuszko
Faculty of Medicine, Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdánsk, Poland
Jacek Mackiewicz
Cancer Genetic Laboratory, Greater Poland Cancer Centre, Poznan, Poland
Rafal Stec
Rustem Safin
Andres Cervantes Ruizperez
Maria de Miguel Luken
Alejandro Falcon
Hospital Universitario Virgen del Rocio, Sevilla, Spain
Elena Garralda Cabanas
Laura Medina
Viver Health, LLC, Morristown, NJ
Víctor Moreno
Luis Paz-Ares Rodríguez
Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid
Christian Britschgi
Eugenio Fernandez
Simon Häfliger
Sacha Rothschild
Martin Forster
Robert Jones
University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
Matthew Krebs
Raid Aljumaily
Kathryn Arbor
Lyudmila Bazhenova
University of California, San Diego, San Diego, CA, US
Timothy Burns
Michael Cheng
Thomas Karasic
Patricia LoRusso
Yale School of Medicine, New Haven, CT
Erminia Massarelli
City of Hope—Comprehensive Cancer Center, Duarte, CA
Pamela Munster
Sai-Hong Ou
Manish Patel
Kenneth K. Yau
Hoffmann-La Roche Limited, Mississauga, Canada
Junko Aimi
Julie Chang
1University of Wisconsin Carbone Cancer Center, Madison, United States
Yoonha Choi
Genentech, Inc, South San Francisco, CA
Neekesh V. Dharia
Genentech, Inc, South San Francisco, CA
Xuefeng Hou
16Roche Products Ltd, Welwyn Garden City, United Kingdom
Tomi Jun
Genentech, Inc, South San Francisco, CA
Mark T. Lin
Genentech, Inc, South San Francisco, CA
Sandhya Mandlekar
Huy Ngo
Nina Qi
Stephanie Royer-Joo
Genentech, Inc, South San Francisco, CA
Jennifer L. Schutzman
Genentech, Inc, South San Francisco, CA
Zhen Shi
Department of Chemistry
Julia Suchomel