Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer

Summary: A phase II study to evaluate antitumor activity of oral cMET inhibitor INC280 in adult patients with EGFR wild-type, advanced non-small cell lung cancer (NSCLC) as measured by overall response rate (ORR). The study will also evaluate safety and pharmacokinetics of INC280.


Eligibility: Inclusion Criteria:
  -  Stage IIIB or IV NSCLC (any histology) at the time of study entry
  -  Histologically or cytologically confirmed diagnosis of NSCLC that is:
  1. EGFR wt as per patient standard of care by a validated test
  2. AND ALK-negative rearrangement as part of the patient standard of care by a validated test
  3. AND (by central assessment) either:
  -  Cohort 1: Pre-treated patients with cMET GCN ≥ 6 or
  -  Cohort 2: Pre-treated patients with cMET GCN ≥4 and < 6, or
  -  Cohort 3: Pre-treated patients with cMET GCN < 4, or
  -  Cohort 4: Pre-treated patients with cMET mutations regardless of cMET GCN, or
  -  Cohort 5: Treatment-naïve patients with cMET dysregulation, or
  -  Cohort 6: Pre-treated patients with either cMET GCN ≥ 10 without cMET mutations or cMET mutations regardless of cMET GCN, or
  -  Cohort 7: Treatment-naïve patients with cMET mutations regardless of cMET GCN
  -  To be eligible for Cohorts 1-4, patients must have failed one or two prior lines of systemic therapy for advanced/metastatic disease
  -  To be eligible for Cohort 6, patients must have failed one prior line of systemic therapy for advanced/metastatic disease
  -  To be eligible for Cohort 5 and Cohort 7, patients must not have received any systemic therapy for advanced/metastatic disease
  -  At least one measurable lesion as defined by RECIST 1.1
  -  Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.
  -  Patients must have adequate organ function
  -  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 HGF inhibitor
  -  Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations
  -  Patients with characterized ALK-positive rearrangement
  -  Clinically significant, uncontrolled heart diseases.
  -  Patients 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 inducers of CYP3A4
  -  Impairment of GI function or GI disease that may significantly alter the absorption of INC280
  -  Patients receiving treatment with any enzyme-inducing anticonvulsant
  -  Applicable to Cohorts 1-4 and Cohort 6 only: Previous anti-cancer and investigational agents within 4 weeks or ≤ 5 x half-life of the agent (whichever is longer) before first dose
  -  Pregnant or nursing women
  -  Women of child-bearing potential, unless they are using highly effective methods of contraception
  -  Sexually active males unless they use a condom during intercourse
  -  Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis
  Other protocol-defined exclusion criteria may apply

Relevance to patient case: not relevant