Novartis Reports 68% Response Rate with MET Inhibitor Capmatinib in Treatment-Naïve NSCLC Patients Harboring MET Exon 14 Skipping Mutations

Novartis recently announced new data and clinical trials for the treatment of non-small cell lung cancer (NSCLC), including the primary efficacy results from the GEOMETYR mono-1 Phase II clinical trial. These results demonstrate that the investigational MET inhibitor capmatinib (INC280) has potential therapeutic effects in patients with locally advanced or metastatic NSCLC harboring MET exon 14 skipping mutations. Currently, there are no approved targeted therapies available for this particularly aggressive form of NSCLC.

The GEOMETRY mono-1 study is an international, prospective, multi-cohort, non-randomized, open-label study that evaluated 97 adult patients with locally advanced or metastatic NSCLC. These patients carried MET exon-14 skipping mutations and were administered 400 mg of capmatinib tablets orally once daily. According to the assessment by the Blinded Independent Review Committee (BIRC), the overall response rates for capmatinib in treatment-naïve patients and previously treated patients were 68% and 41%, respectively. The median duration of response for the two groups was 11.14 months and 9.72 months, respectively.

A special neuroradiological review of patients with brain metastases also revealed intracranial activity in 54% of patients, including cases where brain lesions had completely resolved. All results were based on independent assessments by the Brain Imaging Review Committee (BIRC), and all tumor CT scans were evaluated in parallel by two radiologists to confirm response.

The study showed that the most common treatment-related adverse events (AEs) among all patients included: peripheral edema (42%), nausea (33%), increased creatinine (20%), vomiting (19%), fatigue (14%), decreased appetite (13%), and diarrhea (11%). Most AEs were grade 1/2.

Recently, the U.S. FDA granted Breakthrough Therapy Designation for capmatinib in patients with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations. “The efficacy observed with capmatinib in the GEOMETRY mono-1 trial is promising,” said Dr. Juergen Wolf of University Hospital Cologne. “In addition to the overall response rate in treatment-naïve patients with MET mutations, the duration of response, intracranial activity, and the safety profile of capmatinib represent a significant therapeutic milestone for this patient population. NSCLC patients with MET mutations often require special clinical consideration, as they are typically older and have a poorer prognosis, which further limits treatment options.”

Capmatinib (INC280) is an investigational, oral, and selective MET inhibitor that was licensed by Incyte Corporation to Novartis in 2009. Under the agreement, Incyte granted Novartis exclusive global development and commercialization rights for capmatinib and certain backup compounds across all indications.

References:

Novartis Shows Growing Strength in Lung Cancer Innovation with New Capmatinib Investigational Data and Novel Canakinumab Clinical Trials | BioSpace