Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Stage IIIB or IV NSCLC (any histology) at the time of study entry
  • Histologically or cytologically confirmed diagnosis of NSCLC that is:
  • 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 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
cMET GCN ≥ 6
Pre-treated patients with cMET GCN ≥ 6 treated with INC280 at 400mg BID as second or third line
  • Drug: INC280 (capmatinib)
Experimental
cMET GCN ≥ 4 and < 6
Pre-treated patients with cMET GCN ≥ 4 and < 6 treated with INC280 at 400 mg BID as second or third line
  • Drug: INC280 (capmatinib)
Experimental
cMET GCN < 4
Pre-treated patients with cMET GCN < 4 treated with INC280 at 400mg BID as second or third line
  • Drug: INC280 (capmatinib)
Experimental
cMET mutations
Pre-treated patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID as second or third line
  • Drug: INC280 (capmatinib)
Experimental
cMET dysregulation - treatment-naïve
Treatment-naïve patients with cMET dysregulation treated with INC280 at 400mg BID
  • Drug: INC280 (capmatinib)
Experimental
cMET dysregulation - second line
Pre-treated patients with cMET deregulation treated with INC280 at 400 mg BID as second line
  • Drug: INC280 (capmatinib)
Experimental
cMET mutations treatment-naïve
Treatment-naïve patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID
  • Drug: INC280 (capmatinib)

Recruiting Locations

Massachusetts General Hospital MGH Cancer Center
Boston, Massachusetts 02114
Contact:
Caitlyn Helms
chelms@mgh.harvard.edu

More Details

NCT ID
NCT02414139
Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.