New Data from GEOMETRY mono-1 Study Show Clinically Meaningful Results in Patients with Non-Small Cell Lung Cancer with MET exon-14 Skipping Mutation Treated with Capmatinib
- Primary efficacy analysis demonstrated promising efficacy for capmatinib irrespective of the prior line of therapy in 97 patients: overall response rate was 68 percent and 41 percent and median duration of response was 11.14 months and 9.72 months, respectively, across treatment-naive and previously-treated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring a MET exon-14 skipping mutation
The U.S. Food and Drug Administrationrecently granted capmatinib Breakthrough Therapy designation for the treatment of patients with metastatic NSCLC harboring a MET exon-14 skipping mutation with disease progression on or after platinum-based chemotherapy Novartishas exclusive worldwide development and commercialization rights to capmatinib
Results of the Phase 2 study will be presented at an oral session today,
GEOMETRY mono-1 is an international, prospective, multi-cohort, non-randomized, open-label study evaluating 97 adult patients with locally advanced or metastatic NSCLC harboring a MET exon-14 skipping mutation who received capmatinib tablets 400 mg orally twice daily. Primary efficacy results among treatment-naïve patients (Cohort 5b: 28 patients) included a 68 percent overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1 (95% [CI: [47.6-84.1]) and 41 percent of previously-treated NSCLC patients (Cohort 4: 69 patients) also responded (95% CI: [28.9 - 53.1]). Data on median duration of response (DOR), a key secondary endpoint, was 11.14 months (95% CI: [5.55-NE]) and 9.72 months (95% CI: [5.55-12.98]), in the treatment-naïve and previously-treated groups, respectively. Intracranial activity in 54 percent (n=7/13) of patients, including some cases of complete resolution of brain lesions, was also observed by ad hoc neuro-radiologist review in patients with brain lesions. All results were based on independent assessment by the BIRC, and all tumor CT scans were evaluated in parallel by two radiologists to confirm the response.
The most common treatment-related adverse events (AE) (≥10% all grades) across all cohorts (n=334), were peripheral edema (42%), nausea (33%), creatinine increase (20%), vomiting (19%), fatigue (14%), decreased appetite (13%) and diarrhea (11%); the majority of the AEs were grades 1/2.
“In the absence of approved targeted therapies, patients with advanced or metastatic NSCLC harboring a MET exon-14 skipping mutation must rely on existing treatment approaches and, as a result, face a particularly poor prognosis,” said
About GEOMETRY mono-1
The primary endpoint was ORR based on BIRC assessment per RECIST v1.1. The key secondary endpoint was DOR by BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naïve patients (n=28) of 67.9 percent (95% CI: [47.6 - 84.1]) and an ORR of 40.6 % (95% CI: [28.9 - 53.1]) in the previously treated patients (n=69). Median DOR was 11.14 months (95% CI: [5.55-NE]) in treatment-naïve patients and 9.72 months (95% CI: [5.55-12.98]) in previously treated patients1.
The most common treatment-related AEs included peripheral edema, nausea, creatinine increase and vomiting. Of patients treated with capmatinib, 84 percent experienced an AE, with 36 percent having grade 3/4 AEs (only 4.5% were Grade 4)1.
Capmatinib is an investigational, oral and selective MET inhibitor discovered by
Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding the ongoing clinical development program for capmatinib and its potential in treating NSCLC, Novartis’ plans to submit an NDA for capmatinib and the expected timing of such filing, and whether and when
These forward-looking statements are based on the Company’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments and the risks related to the efficacy or safety of the Company’s development pipeline, the results of further research and development, the high degree of risk and uncertainty associated with drug development, clinical trials and regulatory approval processes, other market or economic factors and competitive and technological advances; and other risks detailed from time to time in the Company’s reports filed with the
2. Salgia R. MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale. Mol Cancer Ther. 2017;16(4):555-565.
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Michael Booth, DPhil
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