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.

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

FIGURE 1

Study design. ECOG PS, Eastern Cooperative Oncology Group performance status; GCN, gene copy number; NSCLC, non–small‐cell lung cancer

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

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

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)