Capmatinib Shows ‘Clinically Meaningful Efficacy’ Against METex14-Mutated NSCLC

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The phase II GEOMETRY mono-1 trial results reported at the 2020 AACR Virtual Annual Meeting I raise the potential for treating advanced non-small-cell lung cancer (NSCLC) with a MET exon 14 skipping mutation (METex14). 

Edward Garon, from the University of California, Los Angeles in the USA, presented results for two of the seven cohorts of patients given capmatinib 400 mg twice daily in the trial. All participants had stage IIIB–IV disease wildtype for EGFR mutations and negative for ALK alterations, but positive for METex14 mutations and/or MET amplification. 

Cohort 4 included 69 METex14-positive patients who had previously received two or three lines of treatment; blinded review committee assessment gave a RECIST overall response rate of 40.6%, all of which were partial responses, and a disease control rate of 78.3%. 

The corresponding rates for the 28 METex14-positive patients in cohort 5b with treatment-naïve NSCLC were 67.9%, including one complete response, and 96.4%. 

Capmatinib induced “rapid and long-lasting responses across both cohorts”, the presenter said. Responses were detected within 7 weeks of treatment in 82.1% of cohort 4 and 68.4% of cohort 5b, and lasted for a median of 9.72 and 11.4 months, respectively. The corresponding 12-month event-free survival rates for the cohorts were 31.8% and 47.3%. 

Furthermore, an intracranial response occurred in seven of the 13 patients with evaluable brain metastases at baseline (median 3.3 lesions). This included complete resolution in four patients, and a combination of complete resolution and stabilisation in three, with all but one of the 13 patients achieving at least stable brain disease. 

“Intracranial responses were as fast as systemic responses”, Edward Garon noted, with all beginning within 6 weeks of treatment initiation. 

Safety analysis of 334 trial participants after a median 14.9 weeks of treatment indicated that grade 3–4 adverse events (AEs) occurred in 35.6%, most commonly peripheral oedema (7.5%) and fatigue (3.0%). Dose adjustments and discontinuation because of treatment-related AEs were required by 21.9% and 11.1% of patients, respectively. 

“Capmatinib is a potent MET inhibitor that has demonstrated clinically meaningful efficacy in advanced NSCLC patients harbouring METex 14 mutations”, the presenter summarised, remarking that the higher response rate in treatment-naïve patients “highlights the importance of early molecular testing”. 

He added that “further validation of the intracranial efficacy of capmatinib is warranted”. 

Reference  

Garon EB, Heist RS, Seto T, et al. Capmatinib in METex14-mutated (mut) advanced non-small-cell lung cancer (NSCLC): Results from the phase II GEOMETRY mono-1 study, including efficacy in patients (pts) with brain metastases (BM). American Association of Cancer Research Virtual Annual Meeting I; 27–28 April 2020 (Abstract CTO82).