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Clinical Trial
. 2021 Apr;112(4):1556-1566.
doi: 10.1111/cas.14826. Epub 2021 Feb 24.

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

Takashi Seto  1 , Kadoaki Ohashi  2 , Shunichi Sugawara  3 , Makoto Nishio  4 , Masayuki Takeda  5 , Keisuke Aoe  6 , Sanae Moizumi  7 , Satoshi Nomura  7 , Takeshi Tajima  7 , Toyoaki Hida  8
Affiliations
Clinical Trial

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

Takashi Seto et al. Cancer Sci. 2021 Apr.

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.

Keywords: MET receptor tyrosine kinase; capmatinib; non-small-cell lung cancer; response; safety.

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Conflict of interest statement

Takashi Seto has received remuneration (≥1 million yen per year) from Precision Medicine Asia (as an employee); lecture fees, honoraria, or other fees (≥500 000 yen per year) from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, MSD, Pfizer Japan, and Taiho Pharmaceutical; and research funds (≥1 million yen per year) from AbbVie, AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, LOXO Oncology, MSD, Nippon Boehringer Ingelheim, Novartis Pharma, Pfizer Japan, and Takeda Pharmaceutical. Shunichi Sugawara has received lecture fees, honoraria, or other fees (≥500 000 yen per year) from AstraZeneca, Chugai Pharmaceutical, MSD, Ono Pharmaceutical, Bristol‐Myers Squibb, and Nippon Boehringer Ingelheim. Makoto Nishio has received lecture fees, honoraria, or other fees (≥500 000 yen per year) from Ono Pharmaceutical, Bristol‐Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Daiichi Sankyo Healthcare, Taiho Pharmaceutical, and Merck Serono; and research funds (≥1 million yen per year) from Novartis Pharma, Ono Pharmaceutical, Chugai Pharmaceutical, Bristol‐Myers Squibb, Taiho Pharmaceutical, Eli Lilly, AstraZeneca, Pfizer, and Astellas. Keisuke Aoe has received lecture fees, honoraria, or other fees (≥500 000 yen per year) from Ono Pharmaceutical; and research funds (≥1 million yen per year) from MSD, AstraZeneca, Ono Pharmaceutical, Kissei, Eli Lilly, Novartis Pharma, Pfizer, and Bristol‐Myers Squibb. Toyoaki Hida has received lecture fees, honoraria, or other fees (≥500 000 yen per year) from AstraZeneca; and research funds (≥1 million yen per year) from Novartis Pharma, AstraZeneca, Pfizer, Servier, and Janssen. Kadoaki Ohashi has received research funds (≥1 million yen per year) from Novartis Pharma. Sanae Moizumi, Satoshi Nomura, and Takeshi Tajima are employees of Novartis Pharma (remuneration of ≥ 1 million yen per year).

Figures

FIGURE 1
FIGURE 1
Study design. ECOG PS, Eastern Cooperative Oncology Group performance status; GCN, gene copy number; NSCLC, non–small‐cell lung cancer
FIGURE 2
FIGURE 2
Waterfall plot showing the best percent change in lesion size according to best overall response (blinded independent review committee assessment) in patients with METΔex14‐mutated non‐small‐cell lung cancer. Data cutoff: April 15, 2019. *Patients still on treatment. †Percent change in target lesion available, but contradicted by overall lesion response = PD or UNK. ‡Received capmatinib as first‐line therapy (cohort 5b). §Received capmatinib as second‐/third‐line therapy (cohort 4). PD, progressive disease; PR, partial response; SD, stable disease; UNK, unknown
FIGURE 3
FIGURE 3
Kaplan‐Meier plots of progression‐free survival (PFS) for the 2/3L group according to blinded independent review committee assessment in patients with METΔex14‐mutated non‐small‐cell lung cancer. The PFS times are reported for both patients in the 1L group. Data cutoff: April 15, 2019. *Received capmatinib as first‐line therapy (cohort 5b). †Received capmatinib as second‐/third‐line therapy (cohort 4). CI, confidence interval; NE, not evaluable
FIGURE 4
FIGURE 4
Swimmer plot showing duration of capmatinib administration and timing of common adverse events (AEs) according to treatment line in 13 patients with METΔex14‐mutated non–small‐cell lung cancer. Data cutoff: September 18, 2019. *Received capmatinib as second‐/third‐line therapy (cohort 4). †Received capmatinib as first‐line therapy (cohort 5b)
See this image and copyright information in PMC

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