GEOMETRY Mono-1 Results: Capmatinib for the Treatment of MET Exon 14–Mutated NSCLC

US Food and Drug Administration–approved capmatinib is an effective second-line treatment for patients with MET exon 14–mutated NSCLC.

MET exon 14–mutated disease is identified in 3% of patients with nonsquamous non–small-cell lung cancer (NSCLC) and represents a clinically unique molecular subtype.¹ In the multicenter, nonrandomized, open-label, multicohort GEOMETRY mono-1 trial, researchers evaluated the oral MET inhibitor capmatinib in patients with MET exon 14–mutated NSCLC.²

GEOMETRY mono-1 enrolled 97 patients with metastatic NSCLC and confirmed MET exon 14 skipping.² Patients were treated with twice-daily oral capmatinib 400 mg until disease progression or unacceptable toxicity was reached.² Key efficacy end points were overall response rate (ORR) and duration of response as determined by blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumours version 1.1.² Other secondary end points included investigator-assessed ORR, duration of response, disease control rate, progression-free survival (PFS; BIRC and investigator assessment), and safety.³

ORR was 68% (median response duration, 12.6 months) among 28 treatment-naïve patients with MET exon 14–mutated NSCLC who received capmatinib during the study.² ORR was 41% (median response duration, 9.7 months) among 69 previously treated patients.²

At the 2020 American Society of Clinical Oncology virtual meeting, researchers reported results for patients who enrolled in the GEOMETRY mono-1 expansion cohort known as Cohort 6.³ These patients had either MET exon 14 mutation, defined as any MET gene copy number (GCN) and disease progression after 1 prior line of systemic therapy, or high-level MET amplification, defined as GCN ≥10.³ There were 34 patients with MET exon 14–mutated NSCLC (N = 31) or high-level MET amplification (N = 3) included in this analysis as of January 6, 2020.³

BIRC assessment resulted in an ORR of 48% (median response duration, 6.9 months) among the 31 patients with MET exon 14–mutated NSCLC (not yet mature; 95% confidence interval [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

Among the 34 patients in Cohort 6, the most common adverse events associated with capmatinib (≥25%, all grades) were peripheral edema (65%), nausea (35%), fatigue (29%), back pain (27%), and vomiting (27%).³

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

References
1. Awad M, et al. J Clin Oncol. 2016;34:721-730.
2. 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 January 11, 2021.
3. Groen H, et al. J Clin Oncol. 2020;38(suppl 15). Abstract 9520.