On June 3, 2019 Incyte (Nasdaq:INCY) reported primary efficacy results from the Novartis-sponsored GEOMETRY mono-1 Phase 2 clinical trial of capmatinib, an investigational, selective MET inhibitor (Press release, Incyte, JUN 3, 2019, View Source [SID1234536781]). The results demonstrate that capmatinib shows promise as a potential treatment option for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that harbor a MET exon-14 skipping mutation. There are currently no approved targeted therapies to treat this particularly aggressive form of NSCLC.

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Results of the Phase 2 study will be presented at an oral session today, June 3, 2019, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2019 Annual Meeting at 8:00 a.m. CDT (Abstract #9004)1.

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 Steven Stein, M.D., Chief Medical Officer, Incyte. "The results of the GEOMETRY mono-1 study to be presented at ASCO (Free ASCO Whitepaper) underscore the potential of capmatinib to meaningfully improve outcomes for this underserved subset of NSCLC patients."

The U.S. Food and Drug Administration (FDA) recently granted capmatinib Breakthrough Therapy designation for patients with metastatic NSCLC harboring a MET exon-14 skipping mutation with disease progression on or after platinum-based chemotherapy. Previously, both the U.S. FDA and Japan’s Pharmaceuticals and Medical Devices Agency recognized capmatinib with Orphan Drug status. It is estimated that 3 to 4 percent of all patients with NSCLC have an identified MET mutation2.

Novartis expects to submit a new drug application to the FDA for capmatinib as a treatment for patients with advanced NSCLC harboring a MET mutation in 2019.

About GEOMETRY mono-1

The Novartis-sponsored GEOMETRY mono-1 trial is an international, prospective, multi-cohort, non-randomized, open-label Phase 2 study to evaluate the efficacy and safety of single-agent capmatinib in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring a MET amplification and/or mutation. Patients with locally advanced or metastatic NSCLC harboring a MET exon-14 skipping mutation (centrally confirmed) were assigned to Cohorts 4 (previously treated patients) or 5B (treatment-naïve), regardless of MET amplification/gene copy number and received 400 mg capmatinib tablets orally twice daily.

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.

About Capmatinib

Capmatinib is an investigational, oral and selective MET inhibitor discovered by Incyte that was licensed to Novartis in 2009. Under the terms of the Agreement, Incyte granted Novartis exclusive worldwide development and commercialization rights to capmatinib and certain back-up compounds in all indications. If capmatinib is successfully developed by Novartis, Incyte may become eligible for over $500 million in future milestones as well as royalties of between 12 and 14 percent on global sales by Novartis.