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Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer.

Authors :
Drilon, A.
Camidge, D. R.
Lin, J. J.
Kim, S.-W.
Solomon, B. J.
Dziadziuszko, R.
Besse, B.
Goto, K.
de Langen, A. J.
Wolf, J.
Lee, K. H.
Popat, S.
Springfeld, C.
Nagasaka, M.
Felip, E.
Yang, N.
Velcheti, V.
Lu, S.
Kao, S.
Dooms, C.
Source :
New England Journal of Medicine. 1/11/2024, Vol. 390 Issue 2, p118-131. 14p.
Publication Year :
2024

Abstract

BACKGROUND The early-generation ROSl tyrosine kinase inhibitors (TKIs) that are approved for the treatment of ROS1 fusion-positive non-small-cell lung cancer (NSCLC) have antitumor activity, but resistance develops in tumors, and intracranial activity is suboptimal. Repotrectinib is a next-generation ROSl TKI with preclinical activity against ROSI fusion-positive cancers, including those with resistance mutations such as ROS1 62032. METHODS In this registrational phase 1-2 trial, we assessed the efficacy and safety of repotrec-tinib in patients with advanced solid tumors, including ROS1 fusion-positive NSCLC. The primary efficacy end point in the phase 2 trial was confirmed objective response; efficacy analyses included patients from phase 1 and phase 2. Duration of response, progression-free survival, and safety were secondary end points in phase 2. RESULTS On the basis of results from the phase 1 trial, the recommended phase 2 dose of repotrectinib was 160 mg daily for 14 days, followed by 160 mg twice daily. Response occurred in 56 of the 71 patients (79°/o; 95°6 confidence interval [CI], 68 to 88) with ROS1 fusion-positive NSCLC who had not previously received a ROS1 TKI; the median duration of response was 34.1 months (95% CI, 25.6 to could not be estimated), and median progression-free survival was 35.7 months (95% CI, 27.4 to could not be estimated). Response occurred in 21 of the 56 patients (3896; 95% CI, 25 to 52) with ROS1 fusion-positive NSCLC who had previously received one ROSl TKI and had never received chemotherapy; the median duration of response was 14.8 months (95% CI, 7.6 to could not be estimated), and median progression-free survival was 9.0 months (95% CI, 6.8 to 19.6). Ten of the 17 patients (5996; 95% CI, 33 to 82) with the ROS1 G2032R mutation had a response. A total of 426 patients received the phase 2 dose; the most common treatment-related adverse events were dizziness (in 58% of the patients), dysgeusia (in 5090), and paresthesia (in 30°6), and 3% discontinued repotrectinib owing to treatment-related adverse events. CONCLUSIONS Repotrectinib had durable clinical activity iii patients with ROS1 fusion-positive NSCLC, regardless of whether they had previously received a ROS1 TKI. Adverse events were mainly of low grade and compatible with long-term administration. (Funded by Turning Point Therapeutics, a wholly owned subsidiary of Bristol Myers Squibb; TRIDENT-1 ClinicalTrials.gov number, NCT03093116.). [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00284793
Volume :
390
Issue :
2
Database :
Academic Search Index
Journal :
New England Journal of Medicine
Publication Type :
Academic Journal
Accession number :
174855766
Full Text :
https://doi.org/10.1056/NEJMoa2302299