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Capmatinib plus gefitinib promising in MET-dysregulated NSCLC
By: News Feed | Last updated: 11th September 2018 | In: China, Lung Cancer, Oncology, Targeted Therapies
AstraZeneca, AZ, capmatinib, cMET, EGFR, gefitinib, INC280, Iressa, Novartis, NSCLC, Oncology
The combination capmatinib (INC280, Novartis) plus gefitinib (Iressa®, AstraZeneca) showed promising, early phase efficacy in patients with mesenchymal-epithelial transition factor (MET)-dysregulated and epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).
Capmatinib is a potent and selective MET-inhibitor. In preclinical studies, capmatinib plus gefitinib showed activity in MET-amplified or overexpressing models of acquired resistance against an EGFR tyrosine kinase inhibitor (TKI).
The Phase Ib/II trial investigated the safety and efficacy of capmatinib plus gefitinib in patients with EGFR-mutated and MET-amplified or -overexpressing NSCLC with disease progression on an EGFR-TKI. Patients in the Phase Ib part (N=61) received a dose of capmatinib ranging from 100 mg once daily (QD) to 600 mg twice daily (BID) plus gefitinib 250 mg QD. Patients in the Phase 2 part (N=100) were treated with the recommended Phase 2 dose (RP2D) resulting from the Phase 1b cohort. The primary efficacy endpoint was the overall response rate (ORR; RECIST 1.1).
The RP2D of capmatinib was 400 mg BID plus gefitinib 250 mg QD. Preliminary signs of clinical activity were observed; the ORR in the combined Phase Ib/II studies was 27%. Moreover, in the Phase 2 patients with high MET-amplified tumours (a MET gene copy number ≥ 6), the ORR was 47%.
Common any-grade treatment-related adverse events (TRAEs) in the Phase Ib/2 study population were nausea (28%), peripheral oedema (22%), decreased appetite (21%), and rash (20%). The most common Grade 3/4 TRAEs included increased amylase (6%) and lipase levels (6%). The authors did not report any significant drug-drug interactions for capmatinib and gefitinib.
Wu YL, et al. J Clin Oncol 2018;doi: 10.1200/JCO.2018.77.7326
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