Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (Geometry Mono-1)

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring Non Small Cell Lung, Non Small Cell Lung Cancer, Non-small cell lung cancer, NSCLC, INC280, EGFR wild-type (wt), advanced non-small cell lung cancer, advanced/metastatic disease, Non-small cell lung carcinoma (NSCLC), treatment of lung cancer after first metastasis, lung cancer, lung adenocarcinoma, Non small cell lung carcinoma, MET exon 14 deletion, METex14del, MET exon 14 skipping, MET exon 14 mutation, MET mutation, MET amplification, MET inhibitor, MET dysregulation, MET activation, MET signaling, MET pathway, met, cMET, Geometry mono-1, Geometry Read More

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