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Phase (Ph) I study of the safety and efficacy of the cMET inhibitor capmatinib (INC280) in patients (pts) with advanced cMET+ non-small cell lung cancer (NSCLC).
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2016
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Pre-clinical PharmacologyOncologyNsclc GroupsMedicinePathologyNsclc PtsImmune Checkpoint InhibitorCmet Inhibitor CapmatinibAnti-cancer AgentCancer TreatmentCmet StatusPharmacologyRadiation OncologyCancer ResearchLung CancerMolecular OncologyMolecular Medicine
9067 Background: cMET dysregulation occurs in 3–10% of NSCLC and is a negative prognostic factor. INC280 is a highly selective cMET inhibitor with preclinical and clinical antitumor activity. The dose-escalation part of this ongoing Ph I study (NCT01324479) included a cMET-dysregulated NSCLC expansion group. Preliminary efficacy was seen in NSCLC pts with high cMET expression, prompting the addition of a second expansion group of pts with EGFRwt, high cMET-expressing NSCLC. We report here on both NSCLC groups. Methods: The primary objective of this Ph I study was met; INC280 RP2D was established at 400 mg BID in a tablet formulation. Secondary objectives included exploring the antitumor activity of INC280 at the RP2D in the original and additional NSCLC groups. Eligible pts (aged ≥ 18 years; ECOG PS ≤ 2) in the original group had documented cMET+ (H-score ≥ 150 or cMET/centromere ratio ≥ 2.0 or gene copy number [GCN] ≥ 5 or IHC 2+ or 3+) NSCLC. In the additional NSCLC group, pts had documented EGFRwt and centrally assessed cMET IHC 3+. Results: As of Sep 28 2015, 43 pts were enrolled in the NSCLC expansion groups: 26 and 17 pts in the original and additional groups, respectively (median age 60 years; 74% Caucasian; 2 median prior therapies; 86% PS 0/1). 27/43 (63%) pts discontinued treatment, mainly due to disease progression (44%). The most common AEs (all grades, regardless of causality) were nausea (47%), vomiting (37%), peripheral edema (35%), decreased appetite (33%), and fatigue (33%). The most common Grade 3/4 AEs (regardless of causality) were anemia, hypokalemia, and pneumonia (all 7%). Response by expansion group and cMET status was assessed in evaluable pts. In the original group, 5/26 pts had partial responses (PR; ORR 19%); 2 pts in the original group also had cMET exon 14 mutations and both had PRs. In pts with cMET IHC 3+, 5/17 had PRs (2 unconfirmed/ongoing; ORR 29%). In pts with cMET GCN ≥ 5, 5/8 had PRs (2 unconfirmed/ongoing; ORR 63%). Conclusions: Oral INC280 at the RP2D was well-tolerated with a manageable safety profile. Strong preliminary activity was observed in pretreated pts with NSCLC and high cMET GCN or cMET overexpression. Clinical trial information: NCT01324479.