Capmatinib in patients with high-level <i>MET</i>-amplified advanced non–small cell lung cancer (NSCLC): results from the phase 2 GEOMETRY mono-1 study.
Juergen Wolf, Tobias R. Overbeck, Ji‐Youn Han, Maximilian J. Hochmair, Filippo de Marinis, Kadoaki Ohashi, Egbert F. Smit, Danielle Power, Edward B. Garon, Harry J.M. Groen, Daniel Shao-Weng Tan, Maeve Waldron-Lynch, Sylvie Le Mouhaër, Ngozi Nwana, Monica Giovannini, Rebecca S. Heist
Abstract
9509 Background: In the ongoing, multicohort, phase 2 GEOMETRY mono-1 study, capmatinib (INC280) has shown efficacy in METex14–mutated NSCLC patients (pts) who were pretreated (cohort 4) or treatment (tx)-naïve (cohort 5b). Here, we report the efficacy and safety of capmatinib in pts with high-level MET-amplified (gene copy number [GCN] ≥10) advanced NSCLC who were either pretreated with 1 or 2 prior lines of systemic therapy (cohort 1a) or tx-naïve (cohort 5a). Methods: Adult pts (≥18 years), ECOG PS 0–1 who had ALK and EGFR wt, stage IIIB/IV (any histology) MET-amplified NSCLC with GCN≥10 received capmatinib 400 mg twice daily (fasting). Primary and key secondary endpoints were overall response rate (ORR) and duration of response (DOR), respectively, by blinded independent review committee (BIRC) assessment per RECIST v1.1. Other secondary endpoints included investigator-assessed ORR, DOR, disease control rate (DCR), progression-free survival (PFS, BIRC and investigator assessment), overall survival, and safety. Results: As of Jan 06, 2020, 84 pts were evaluable for efficacy (cohort 1a [2 nd /3 rd line], 69 pts; Cohort 5a [1 st line], 15 pts). Tx was ongoing for 3 pts in cohort 1a, none in cohort 5a. Per BIRC assessment in cohorts 1a and 5a, respectively, ORR was 29% and 40%, median DOR was 8.31 months (mo, 20 responders, 95% CI: 4.17–15.44) and 7.54 mo (6 responders, 95% CI: 2.56–14.26), and median PFS was 4.07 (95% CI: 2.86–4.83) and 4.17 (95% CI: 1.45–6.87) mo. Investigator assessment was in line with BIRC assessment (Table). The most common adverse events across all cohorts (≥25%, all grades, N = 364) were peripheral edema (51.1%), nausea (44.8%) and vomiting (28.0%). Data for biomarker analysis and pts with brain metastasis will be presented at the ASCO 2020 meeting. Conclusion: Capmatinib has demonstrated activity in the subset of pts with high-level MET-amplified (GCN≥10) NSCLC, with a higher response rate in tx-naïve pts. Safety profile remains favorable and similar to previous reports of capmatinib. Clinical trial information: NCT02414139 . [Table: see text]