Adrian G Sacher,Wilson H Miller,Manish R Patel,Luis Paz-Ares,Armando Santoro,Myung-Ju Ahn,Rafal Dziadziuszko,Pierre Freres,Jia Luo,Samantha Bowyer,Jayesh Desai,Ben Markman,Maria De Miguel,Sanjeev Deva,Alejandro Falcon,Guzman Alonso,João Daniel Guedes,Se Hyun Kim,Matthew G 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, ,
{"title":"单药Divarasib治疗KRAS g12c阳性非小细胞肺癌:一项I期研究的长期随访","authors":"Adrian G Sacher,Wilson H Miller,Manish R Patel,Luis Paz-Ares,Armando Santoro,Myung-Ju Ahn,Rafal Dziadziuszko,Pierre Freres,Jia Luo,Samantha Bowyer,Jayesh Desai,Ben Markman,Maria De Miguel,Sanjeev Deva,Alejandro Falcon,Guzman Alonso,João Daniel Guedes,Se Hyun Kim,Matthew G 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, , ","doi":"10.1200/jco-25-00040","DOIUrl":null,"url":null,"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.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"13 1","pages":"JCO2500040"},"PeriodicalIF":42.1000,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Single-Agent Divarasib in Patients With KRAS G12C-Positive Non-Small Cell Lung Cancer: Long-Term Follow-Up of a Phase I Study.\",\"authors\":\"Adrian G Sacher,Wilson H Miller,Manish R Patel,Luis Paz-Ares,Armando Santoro,Myung-Ju Ahn,Rafal Dziadziuszko,Pierre Freres,Jia Luo,Samantha Bowyer,Jayesh Desai,Ben Markman,Maria De Miguel,Sanjeev Deva,Alejandro Falcon,Guzman Alonso,João Daniel Guedes,Se Hyun Kim,Matthew G 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, , \",\"doi\":\"10.1200/jco-25-00040\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":\"13 1\",\"pages\":\"JCO2500040\"},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2025-07-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/jco-25-00040\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/jco-25-00040","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Single-Agent Divarasib in Patients With KRAS G12C-Positive Non-Small Cell Lung Cancer: Long-Term Follow-Up of a Phase I Study.
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.
期刊介绍:
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.