Clinical Trials /

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

NCT02414139

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: CINC280A2201
  • SECONDARY ID: 2014-003850-15
  • NCT ID: NCT02414139

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
INC280 (capmatinib)cMET GCN ≥ 6

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.

Trial Arms

NameTypeDescriptionInterventions
cMET GCN ≥ 6ExperimentalPre-treated patients with cMET GCN ≥ 6 treated with INC280 at 400mg BID as second or third line
  • INC280 (capmatinib)
cMET GCN ≥ 4 and < 6ExperimentalPre-treated patients with cMET GCN ≥ 4 and < 6 treated with INC280 at 400 mg BID as second or third line
  • INC280 (capmatinib)
cMET GCN < 4ExperimentalPre-treated patients with cMET GCN < 4 treated with INC280 at 400mg BID as second or third line
  • INC280 (capmatinib)
cMET mutationsExperimentalPre-treated patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID as second or third line
  • INC280 (capmatinib)
cMET dysregulation - treatment-naïveExperimentalTreatment-naïve patients with cMET dysregulation treated with INC280 at 400mg BID
  • INC280 (capmatinib)
cMET dysregulation - second lineExperimentalPre-treated patients with cMET deregulation treated with INC280 at 400 mg BID as second line
  • INC280 (capmatinib)
cMET mutations treatment-naïveExperimentalTreatment-naïve patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID
  • INC280 (capmatinib)

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:at least 18 weeks
Safety Issue:
Description:Proportion of patients with a best overall response defined as complete response (CR) or partial response (PR) by Blinded Independent Review Committee (BIRC) assessment per RECIST 1.1

Secondary Outcome Measures

Measure:Duration of Response (DOR) - Key Secondary
Time Frame:at least 18 weeks
Safety Issue:
Description:Calculated as the time from the date of the first documented CR or PR by Blinded Independent Review Committee (BIRC) per RECIST 1.1 to the first documented progression or death due to any cause for patients with PR or CR.
Measure:Overall Response Rate (ORR)
Time Frame:at least 18 weeks
Safety Issue:
Description:ORR (complete response (CR)+ partial response (PR)) per RECIST 1.1 by investigator assessment
Measure:Duration of Response (DOR)
Time Frame:at least 18 weeks
Safety Issue:
Description:DOR per RECIST 1.1 by investigator assessment
Measure:Time to Response (TTR)
Time Frame:at least 18 weeks
Safety Issue:
Description:TTR per RECIST 1.1 both by BIRC and investigator assessment
Measure:Disease Control Rate (DCR)
Time Frame:at least 18 weeks
Safety Issue:
Description:DCR per RECIST 1.1 both by BIRC and investigator assessment
Measure:Progression-free Survival (PFS)
Time Frame:at least 18 weeks
Safety Issue:
Description:PFS per RECIST 1.1 both by BIRC and investigator assessment
Measure:Overall Survival (OS)
Time Frame:at least 18 weeks
Safety Issue:
Description:OS, defined as time from first dose of INC280 to death due to any cause
Measure:Number of patients with incidence of adverse events and serious adverse events, change in vital signs, laboratory results (hematology, blood chemistry, and urinalysis) and ECG.
Time Frame:at least 18 weeks
Safety Issue:
Description:Safety of INC280
Measure:Cmax, Cmin and plasma concentration-time profiles of INC280
Time Frame:6 weeks
Safety Issue:
Description:Pharmacokinetics of INC280 and metabolite CMN288

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • 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
  • MET exon 14 skipping
  • MET exon 14 mutation
  • MET mutation
  • MET amplification
  • MET inhibitor
  • MET dysregulation
  • MET activation
  • MET signaling
  • MET pathway
  • met
  • cMET

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