TY - JOUR
T1 - Capmatinib in Japanese patients with MET exon 14 skipping–mutated or MET-amplified advanced NSCLC
T2 - GEOMETRY mono-1 study
AU - Seto, Takashi
AU - Ohashi, Kadoaki
AU - Sugawara, Shunichi
AU - Nishio, Makoto
AU - Takeda, Masayuki
AU - Aoe, Keisuke
AU - Moizumi, Sanae
AU - Nomura, Satoshi
AU - Tajima, Takeshi
AU - Hida, Toyoaki
N1 - Funding Information:
We would like to thank the patients, their families and caregivers, and the clinical staff at each site for participating in this study. This study was funded by Novartis. The authors thank Nicholas D. Smith (EMC KK) for medical writing support, which was funded by Novartis.
Publisher Copyright:
© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - MET receptor tyrosine kinase
KW - capmatinib
KW - non–small-cell lung cancer
KW - response
KW - safety
UR - http://www.scopus.com/inward/record.url?scp=85101544142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101544142&partnerID=8YFLogxK
U2 - 10.1111/cas.14826
DO - 10.1111/cas.14826
M3 - Article
C2 - 33506571
AN - SCOPUS:85101544142
VL - 112
SP - 1556
EP - 1566
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 4
ER -
