Guilherme Harada MD , Fernando C. Santini MD , Clare J. Wilhelm PhD , Rebecca W. Repetti NP , Jason C. Chang MD , Soo-Ryum Yang MD , Yun-Te Lin MSc , Khadeja A. Moses BA , Christina Falcon MPH, PMP , Michelle Goldstein MSW , Alex Makhnin MA , Michelle S. Ginsberg MD , Andrew J. Plodkowski MD , Mark G. Kris MD , Alexander Drilon MD
{"title":"A Phase II Study of Cabozantinib in Patients With MET-Altered Lung Cancers","authors":"Guilherme Harada MD , Fernando C. Santini MD , Clare J. Wilhelm PhD , Rebecca W. Repetti NP , Jason C. Chang MD , Soo-Ryum Yang MD , Yun-Te Lin MSc , Khadeja A. Moses BA , Christina Falcon MPH, PMP , Michelle Goldstein MSW , Alex Makhnin MA , Michelle S. Ginsberg MD , Andrew J. Plodkowski MD , Mark G. Kris MD , Alexander Drilon MD","doi":"10.1016/j.jtocrr.2025.100857","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Only type I MET tyrosine kinase inhibitors (TKIs) are approved for treating <em>MET</em>-altered NSCLCs. Preclinically, type II TKIs, such as cabozantinib, can rescue progression on type I TKIs. This phase 2 trial (NCT01639508) evaluated the activity of cabozantinib in patients with MET-dependent lung cancers, including TKI-pretreated cancers.</div></div><div><h3>Methods</h3><div>This phase 2 trial with a Simon two-stage minimax design treated patients with metastatic, <em>MET</em>-altered lung cancers with cabozantinib (60 mg daily) until progression or intolerable toxicity. The primary end point was objective response rate (ORR). We prespecified that cabozantinib would be considered a useful agent if at least a 20% ORR was observed. Secondary end points included progression-free survival, overall survival, and safety.</div></div><div><h3>Results</h3><div>We enrolled 28 patients, 23 patients (82%) with only a <em>MET</em> exon 14 alteration, two patients (7%) with <em>MET</em> amplification, and three patients (11%) with concurrent <em>MET</em> exon 14 alteration and amplification. There were 24 patients (86%) previously treated with a type I MET TKI. The ORR was 20% (5/25 assessable patients; 95% confidence interval [CI]: 8.9%–39.1%), with five partial responses (duration ranged from 4 to 39 mo). Four of five responders were type I MET TKI pretreated. The median progression-free survival and overall survival were 4.5 (95% CI: 3.3–5.7) months and 7.2 (95% CI: 2.9–11.5) months, respectively. Dose modification and discontinuation occurred in 64% (18/28) and 7% (2/28) of patients, respectively.</div></div><div><h3>Conclusion</h3><div>This trial met its primary end point. Importantly, we demonstrated that cabozantinib, a type II MET TKI, could benefit patients with MET-altered lung cancers previously treated with type I MET TKIs.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100857"},"PeriodicalIF":3.0000,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JTO Clinical and Research Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666364325000748","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction
Only type I MET tyrosine kinase inhibitors (TKIs) are approved for treating MET-altered NSCLCs. Preclinically, type II TKIs, such as cabozantinib, can rescue progression on type I TKIs. This phase 2 trial (NCT01639508) evaluated the activity of cabozantinib in patients with MET-dependent lung cancers, including TKI-pretreated cancers.
Methods
This phase 2 trial with a Simon two-stage minimax design treated patients with metastatic, MET-altered lung cancers with cabozantinib (60 mg daily) until progression or intolerable toxicity. The primary end point was objective response rate (ORR). We prespecified that cabozantinib would be considered a useful agent if at least a 20% ORR was observed. Secondary end points included progression-free survival, overall survival, and safety.
Results
We enrolled 28 patients, 23 patients (82%) with only a MET exon 14 alteration, two patients (7%) with MET amplification, and three patients (11%) with concurrent MET exon 14 alteration and amplification. There were 24 patients (86%) previously treated with a type I MET TKI. The ORR was 20% (5/25 assessable patients; 95% confidence interval [CI]: 8.9%–39.1%), with five partial responses (duration ranged from 4 to 39 mo). Four of five responders were type I MET TKI pretreated. The median progression-free survival and overall survival were 4.5 (95% CI: 3.3–5.7) months and 7.2 (95% CI: 2.9–11.5) months, respectively. Dose modification and discontinuation occurred in 64% (18/28) and 7% (2/28) of patients, respectively.
Conclusion
This trial met its primary end point. Importantly, we demonstrated that cabozantinib, a type II MET TKI, could benefit patients with MET-altered lung cancers previously treated with type I MET TKIs.