Clinical Trial 18398

Cancer Type: Thoracic
Interventions:INC280 (Capmatinib)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Jhanelle Gray

Overview

Study Title

Novartis Pharmaceuticals trial entitled: A phase II, multicenter, study of oral cMET inhibitor INC280 in adult patients with EGFR wild-type (wt), advanced non-small cell lung cancer (NSCLC)

Summary

The purpose of this study is to learn whether the drug INC280 helps to control lung cancer, and whether it is safe when given to patients suffering from Non-small Cell Lung Cancer (NSCLC) who have received one or two prior therapies for their advanced cancer.

Objective

Primary Objective: The primary objective is to demonstrate the antitumor activity of INC280, as measured by overall response rate (ORR) to INC280 by Blinded Independent Review Committee (BIRC) assessment, by cohort. Secondary Objectives: Objective 1: To evaluate ORR and DOR by investigator assessment, by cohort. Objective 2: To evaluate time to response (TTR), disease control rate (DCR) and progression-free survival (PFS) by investigator and by BIRC assessment, by cohort. Objective 3: To evaluate overall survival (OS), by cohort. Objective 4: To evaluate INC280 safety profile as monotherapy in NSCLC patients who have received one or two prior lines of systemic therapy in advanced/metastatic setting. Objective 5: To characterize the pharmacokinetics of INC280.

Inclusion Criteria

  • Age 18 years or older
  • Stage IIIB or IV NSCLC, any histology, at the time of study entry
  • Histologically or cytologically confirmed diagnosis of NSCLC that is: epidermal growth factor receptor (EGFR) wt as per patient standard of care by a validated test; AND ALK-negative rearrangement as part of the patient standard of care by a validated test; AND (by central assessment) either: Cohort 1: pre-treated with cMET GCN ≥ 6, or Cohort 2: pre-treated with cMET GCN ≥4 and less than 6, or Cohort 3: pre-treated with cMET GCN less than 4, or Cohort 4: Pre-treated with cMET mutations regardless of cMET GCN, Cohort 5: pre-treated with cMET dysregulation..
  • Cohorts 1-4: Must have failed one or two prior lines of systemic therapy
  • Cohort 5: Must not have received any systemic therapy for advanced/metastatic disease (stage IIIB or IV NSCLC). Neo-adjuvant and adjuvant systemic therapies will not count as one prior line of treatment if relapse occurred > 12 months from the end of the neo-adjuvant or adjuvant systemic therapy.
  • At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. Patients with any grade of alopecia are allowed to enter the study.
  • Must have adequate organ function
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • Details and other protocol-defined inclusion criteria may apply

  • Exclusion Criteria

  • Prior treatment with crizotinib, or any other cMET or hepatic growth factor (HGF) inhibitor
  • Characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations.
  • Potential participants with characterized ALK-positive rearrangement
  • Clinically significant, uncontrolled heart diseases
  • Receiving treatment with medications that cannot be discontinued at least 1 week prior to first INC280 treatment and for the duration of the study: Strong and moderate inhibitors of CYP3A4; Strong inducers of CYP3A4.
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of INC280
  • Receiving treatment with any enzyme-inducing anticonvulsant
  • Cohorts 1-4 only: Previous anti-cancer and investigational agents within 4 weeks or ≤ 5 x half-life of the agent (whichever is longer) before first dose of INC280. If previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 4 weeks before first dose of INC280. If previous treatment is an oral targeted agent, then the treatment must be discontinued after at least 5 x half-life of the agent before the first dose of INC280.
  • Women of child-bearing potential, unless they are using highly effective methods of contraception
  • Women who are pregnant of breastfeeding
  • Sexually active males unless they use a condom during intercourse
  • Other protocol-defined exclusion criteria may apply