Capmatinib for Patients with NSCLC with MET Exon 14 Mutation

Capmatinib is the first therapy approved for use in patients with MET exon 14-mutated metastatic NSCLC.

Identified in 3% of patients with nonsquamous NSCLC, mesenchymal-epithelial transition (MET) exon 14-mutated disease represents a clinically unique molecular subtype.¹ Capmatinib (Tabrecta), an oral agent that inhibits MET, was evaluated in patients with MET exon 14-mutated NSCLC in the GEOMETRY mono-1 trial.²

GEOMETRY mono-1 was a multicenter, nonrandomized, open-label, multicohort study that enrolled 97 patients with metastatic NSCLC and confirmed MET exon 14 skipping. In this trial, patients received capmatinib 400 mg orally twice daily until disease progression or unacceptable toxicity.^2,3 Key efficacy end points were ORR and DOR by BIRC per Response Evaluation Criteria in Solid Tumors version 1.1. Other secondary end points included investigator-assessed ORR, DOR, DCR, PFS (BIRC and investigator assessment), and safety.^2,3

Among 28 treatment-naïve patients with MET exon 14-mutated NSCLC who received capmatinib in GEOMETRY mono-1, the ORR was 68% with a median DOR of 12.6 months.² Among 69 previously treated patients, ORR was 41% with a median DOR of 9.7 months.²

During the 2020 American Society of Clinical Oncology meeting, researchers reported results for patients who enrolled in the expansion cohort, cohort 6, of GEOMETRY mono-1. These patients had either high-level MET amplification, defined as gene copy number ≥10, or MET exon 14 mutation (any MET gene copy number) and disease progression after 1 previous line of systemic therapy.³ As of January 6, 2020, 34 patients with MET exon 14-mutated NSCLC (N = 31) or high-level MET amplification (N = 3) were included in this analysis.³ Treatment was ongoing for 38% of patients.³

Among the 31 patients with MET exon 14-mutated NSCLC, blinded assessment resulted in an ORR of 48% with median DOR of 6.9 months (not yet mature, 95% CI, 4.2-not evaluable).³ The median PFS was 8.1 months (not yet mature, 95% CI, 4.2-9.9).³ Among the 3 patients with high-level MET amplification, all had stable disease per blinded assessment and were on treatment for 48, 85, and 97 days.³

The most common AEs associated with capmatinib among the 34 patients in cohort 6 (≥25%, all grades) were peripheral edema (65%), nausea (35%), fatigue (29%), back pain (27%), and vomiting (27%).³ Data among this cohort of patients who took capmatinib without fasting restrictions confirm the drug’s favorable safety profile.³

Based on the results of GEOMETRY mono-1, researchers concluded that capmatinib is efficacious in the second-line treatment of patients with MET exon 14-mutated NSCLC.³ The drug was approved for use by the US Food and Drug Administration in May 2020.²

References
1. Awad MM, Oxnard GR, Jackman DM, et al. MET exon 14 mutations in non–small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J Clin Oncol. 2016;34:721-730.
2. US Food and Drug Administration. FDA grants accelerated approval to capmatinib for metastatic non-small cell lung cancer. May 6, 2020. www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-capmatinib-metastatic-non-small-cell-lung-cancer. Accessed November 30, 2020.
3. Groen HJM, Akerley WL, Souquet PJ, et al. Capmatinib in patients with METex14-mutated or high-level MET-amplified advanced non–small-cell lung cancer (NSCLC): results from cohort 6 of the phase 2 GEOMETRY mono-1 study. J Clin Oncol. 2020:38(15_suppl). Abstract 9520.