As reported in The Lancet Oncology by Wolf et al, the final results of the phase II GEOMETRY mono-1 trial support the activity of the kinase inhibitor capmatinib in patients with non–small cell lung cancer (NSCLC) with MET exon 14–skipping mutation (METex14).
Study Details
The multicohort trial included 160 patients with METex14-positive, EGFR wild-type, and ALK rearrangement–negative disease enrolled between June 2015 and March 2020 at sites in 20 countries. Patients received capmatinib at 400 mg twice daily in 21-day cycles. Of the 160 patients, 60 were treatment-naive, and 100 had received previous treatment. The primary outcome measure was objective response rate on blinded independent central review.
Key Findings
Median follow-up was 46.4 months (interquartile range [IQR] = 41.8–65.4 months) in the treatment-naive group and 66.9 months (IQR = 56.7–73.9 months) in the previously treated group.
Among 60 treatment-naive patients, objective responses were observed in 41 (68%, 95% confidence interval [CI] = 55.0%–79.7%), including a complete response in 3 (5%). Median duration of response was 16.6 months (95% CI = 8.4–22.1 months). The disease control rate was 98%. Median progression-free survival was 12.5 months (95% CI = 8.3–18.0 months). Median overall survival was 21.4 months (95% CI = 15.2–30.5 months).
Among 100 previously treated patients, objective responses were observed in 44 (44%, 95% CI = 34.1%–54.3%), with a complete response in 1 (1%). Median duration of response was 9.7 months (95% CI = 5.6–13.0 months). The disease control rate was 82%. Median progression-free survival was 5.5 months (95% CI = 4.2–8.1 months). Median overall survival was 16.8 months (95% CI = 11.6–23.8 months).
Among the 160 patients, median duration of exposure to capmatinib was 34.9 weeks (IQR = 13.0–80.6 weeks). Grade 3 or 4 adverse events occurred in 73%, most commonly peripheral edema (17%) and increased lipase (9%). Treatment-related serious adverse events were reported in 17% of patients. Treatment-related adverse events led to treatment discontinuation in 16%. Treatment-related death occurred in four patients, from cardiac arrest, hepatitis, organizing pneumonia, and pneumonitis in one patient each.
The investigators concluded: “These long-term results support METex14 as a targetable oncogenic driver in NSCLC and add to the evidence supporting capmatinib as a targeted treatment option for treatment-naive and previously treated patients with METex14 NSCLC.”
Jürgen Wolf, MD, of the Center for Integrated Oncology, University Hospital of Cologne, Germany, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Novartis Pharmaceuticals. For full disclosures of the study authors, visit thelancet.com.
