Final results from the phase II GEOMETRY mono-1 trial, published in The Lancet Oncology, demonstrate the sustained efficacy of capmatinib in patients with non-small cell lung cancer (NSCLC) harboring MET exon 14-skipping mutations (MET ex14). The multicenter study, conducted across 20 countries, enrolled patients between June 2015 and March 2020, solidifying MET ex14 as a key target.
Study Design and Patient Population
The trial included 160 patients with MET ex14-positive, EGFR wild-type, and ALK rearrangement–negative disease. Participants were administered capmatinib at 400 mg twice daily in 21-day cycles. The cohort comprised 60 treatment-naive patients and 100 patients who had received prior treatment. The primary endpoint was objective response rate as assessed by blinded independent central review.
Efficacy Outcomes
After a median follow-up of 46.4 months (IQR = 41.8–65.4 months) in the treatment-naive group, the objective response rate was 68% (95% CI = 55.0%–79.7%), with 3 patients (5%) achieving complete responses. The median duration of response was 16.6 months (95% CI = 8.4–22.1 months), and the disease control rate was 98%. Median progression-free survival was 12.5 months (95% CI = 8.3–18.0 months), and median overall survival reached 21.4 months (95% CI = 15.2–30.5 months).
In the previously treated group, with a median follow-up of 66.9 months (IQR = 56.7–73.9 months), the objective response rate was 44% (95% CI = 34.1%–54.3%), with 1 patient (1%) achieving a complete response. The median duration of response was 9.7 months (95% CI = 5.6–13.0 months), and the disease control rate was 82%. Median progression-free survival was 5.5 months (95% CI = 4.2–8.1 months), and median overall survival was 16.8 months (95% CI = 11.6–23.8 months).
Safety Profile
The median duration of exposure to capmatinib across all 160 patients was 34.9 weeks (IQR = 13.0–80.6 weeks). Grade 3 or 4 adverse events were observed in 73% of patients, with peripheral edema (17%) and increased lipase (9%) being the most common. Treatment-related serious adverse events occurred in 17% of patients, leading to treatment discontinuation in 16%. Treatment-related deaths were reported in four patients due to cardiac arrest, hepatitis, organizing pneumonia, and pneumonitis.
Expert Commentary
The study's corresponding author, Jürgen Wolf, MD, of the Center for Integrated Oncology, University Hospital of Cologne, Germany, and his colleagues concluded that these findings reinforce MET ex14 as a targetable oncogenic driver in NSCLC. The data support capmatinib as a targeted treatment option for both treatment-naive and previously treated patients with MET ex14 NSCLC.
