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Therapeutic efficacy of Capmatinib

Metastatic NSCLC with a Mutation that Leads to MET Exon 14 Skipping

The efficacy of Capmatinib was evaluated in GEOMETRY mono-1, a multicenter, non-randomized, open-label, multicohort study (NCT02414139). Eligible patients were required to have NSCLC with a mutation that leads to MET exon 14  skipping, epidermal growth factor receptor (EGFR) wild-type and anaplastic lymphoma kinase (ALK) negative status, and  at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients  with symptomatic CNS metastases, clinically significant uncontrolled cardiac disease, or who received treatment with any  MET or hepatocyte growth factor (HGF) inhibitor were not eligible for the study.

Out of the first 97 patients enrolled in GEOMETRY mono-1 following the central confirmation of MET exon 14 skipping  by a RNA-based clinical trial assay, 78 patient samples were retested with the FDA-approved FoundationOne® CDx (22  treatment-naïve and 56 previously treated patients) to detect mutations that lead to MET exon 14 skipping. Out of 78 samples retested with FoundationOne® CDx, 73 samples were evaluable (20 treatment-naïve and 53 previously treated  patients), 72 (20 treatment-naïve and 52 previously treated patients) of which were confirmed to have a mutation that  leads to MET exon 14 skipping, demonstrating an estimated positive percentage agreement of 99% (72/73) between the  clinical trial assay and the FDA-approved assay.

Patients received Capmatinib 400 mg orally twice daily until disease progression or unacceptable toxicity. The major  efficacy outcome measure was overall response rate (ORR) as determined by a Blinded Independent Review Committee  (BIRC) according to RECIST 1.1. An additional efficacy outcome measure was duration of response (DOR) by BIRC.

The efficacy population included 60 treatment-naïve patients and 100 previously treated patients. The median age was 71  years (range: 48 to 90 years); 61% female; 77% White; 25% had Eastern Cooperative Oncology Group (ECOG)  Performance Status (PS) 0 and 74% had ECOG PS 1; 61% never smoked; 83% had adenocarcinoma; and 16% had CNS  metastases. Among previously treated patients, 81% received one, 16% received two and 3% received three prior lines of  systemic therapy. Amongst previously treated patients, 86% received prior platinum-based chemotherapy.

Efficacy results are presented in Table 5.

from FDA,2023.03