MET-mutations and MET-amplifications are reported in 1-6% of patients with NSCLC. In the ongoing, multicohort phase 2 GEOMETRY trial, patients with stage III/IV NSCLC and high-level MET-amplification (gene copy number >10) respond well to capmatinib, a highly potent and selective inhibitor of the MET receptor tyrosine kinase, researchers reported at the virtual meeting of the American Society of Clinical Oncology.

In the GEOMETRY trial, 84 patients with high-level MET-amplification (ALK and EGFR wild-type, stage IIIB/IV) received capmatinib 400 mg twice daily (n=15 were treatment-naïve, n=69 were second or third-line). The primary endpoint of the trial was the objective response rate (ORR), while secondary endpoints were duration of response (DOR), progression-free survival (PFS) and overall survival (OS).

“The ORR in the treatment-naïve patients was 40%, and 29% in the pre-treated patients”, reported  Prof. Jürgen Wolf, University Hospital Cologne, Germany. “In the majority of patients these were partial responses.” In addition, 40.6% of the pre-treated patients and 26.7% of the treatment-naïve patients showed stable disease, which results in a disease control rate of 71% and 66.7%, respectively. “The response rates observed in patients with high-level MET-amplification are more moderate compared with MET exon14 skipping mutation cohorts”, said Prof. Wolf.

Median DOR was 8.31 months and 7.54 months and median PFS was 4.07 and 4.17 months  in pre-treated and treatment-naïve patients, respectively. Median OS was 10.61 and 9.56 months in pre-treated and treatment-naïve patients, respectively. Capmatinib was well tolerated with a favorable safety profile, consistent with previous reports. “The most frequently observed toxicity was peripheral edema, nausea, vomiting, decreased appetite, and diarrhea”, reported Prof. Wolf.

“In conclusion, these results show that capmatinib demonstrates clinical activity in patients with high-level MET-amplification NSCLC. As is the case in patients with MET exon 14-skipping mutation NSCLC, response rates seems somewhat higher in treatment-naïve patients compared with pre-treated patients.”

 

Wolf J, et al. ASCO 2020 virtual meeting, abstract 9509