Capmatinib in Japanese patients with MET exon 14 skipping-mutated or MET-amplified advanced NSCLC: GEOMETRY mono-1 study.

Abstract

MET mutations leading to exon 14 skipping (METΔex14) are strong molecular drivers for non-small-cell lung cancer (NSCLC). Capmatinib is a highly potent, selective oral MET inhibitor that showed clinically meaningful efficacy and a manageable safety profile in a global phase II study (GEOMETRY mono-1, NCT02414139) in patients with advanced METΔex14-mutated/MET-amplified NSCLC. We report results of preplanned analyses of 45 Japanese patients according to MET status (METΔex14-mutated or MET-amplified) and line of therapy (first- [1L] or second-/third-line [2/3L]). The starting dose was 400 mg twice daily. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent review committee. A key secondary endpoint was duration of response (DOR). Among METΔex14-mutated patients, in the 1L group, one patient achieved partial response (DOR of 4.24 months) and the other had stable disease. In the 2/3L group, the ORR was 36.4% (95% confidence interval [CI] 10.9%-69.2%), median DOR was not evaluable, and progression-free survival was 4.70 months. One patient (2/3L group) showed partial resolution of brain lesions per independent neuroradiologist review. In MET-amplified patients with a MET gene copy number of ≥10, the ORR was 100% (2/2 patients) in the 1L group and 45.5% (5/11 patients) in the 2/3L group, with DOR of 8.2 and 8.3 months, respectively. Common treatment-related adverse events among the 45 Japanese patients were blood creatinine increased (53.3%), nausea (35.6%), and oedema peripheral (31.1%); most were grade 1/2 severity. In conclusion, capmatinib was effective and well tolerated by Japanese patients with METΔex14/MET-amplified NSCLC, consistent with the overall population.

• Authors: Takashi Seto, Kadoaki Ohashi, Shunichi Sugawara, Makoto Nishio, Masayuki Takeda, Keisuke Aoe, Sanae Moizumi, Satoshi Nomura, Takeshi Tajima, Toyoaki Hida
• Journal: Cancer science (Cancer Sci) Vol. 112 Issue 4 Pg. 1556-1566 (Apr 2021) ISSN: 1349-7006 [Electronic] England
• PMID: 33506571 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Benzamides
• Imidazoles
• Protein Kinase Inhibitors
• Triazines
• MET protein, human
• Proto-Oncogene Proteins c-met
• capmatinib

Topics

• Aged
• Aged, 80 and over
• Benzamides
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Exons (genetics)
• Female
• Humans
• Imidazoles (therapeutic use)
• Japan
• Lung Neoplasms (drug therapy, genetics)
• Male
• Mutation
• Protein Kinase Inhibitors (therapeutic use)
• Proto-Oncogene Proteins c-met (genetics)
• Triazines (therapeutic use)