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A Safety and Efficacy Study of INC280 Alone, and in Combination With Erlotinib, Compared to Chemotherapy, in Advanced/Metastatic Non-small Cell Lung Cancer Patients With EGFR Mutation and cMET Amplification

NCT02468661

Description:

The purpose of this study was to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of INC280 in combination with erlotinib in the Phase Ib of this study, and to assess the anti-tumor activity and safety of INC280 alone, and in combination with erlotinib, versus platinum with pemetrexed in the Phase II of this study, in adult patients with EGFR mutated, cMET amplified, advanced/metastatic non-small cell lung cancer with acquired resistance to prior EGFR TKI.

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

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Safety and Efficacy Study of INC280 Alone, and in Combination With Erlotinib, Compared to Chemotherapy, in Advanced/Metastatic Non-small Cell Lung Cancer Patients With EGFR Mutation and cMET Amplification
  • Official Title: A Phase Ib/II, Open-label, Multicenter Trial With Oral cMET Inhibitor INC280 Alone and in Combination With Erlotinib Versus Platinum With Pemetrexed in Adult Patients With EGFR Mutated, cMET-amplified, Locally Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC) With Acquired Resistance to Prior EGFR Tyrosine Kinase Inhibitor (EGFR TKI)

Clinical Trial IDs

  • ORG STUDY ID: CINC280B2201
  • NCT ID: NCT02468661

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
INC280 single agentINC280 single agent
INC280 in combination with erlotinibINC280 in combination with erlotinib
Platinum/pemetrexedPlatinum in combination with pemetrexed

Purpose

The purpose of this study is to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of INC280 in combination with erlotinib in the Phase Ib of this study, and to assess the anti-tumor activity and safety of INC280 alone, and in combination with erlotinib, versus platinum with pemetrexed in the Phase II of this study, in adult patients with EGFR mutated, cMET amplified, advanced/metastatic non-small cell lung cancer with acquired resistance to prior EGFR TKI.

Detailed Description

      The decision was taken to halt study enrollment with Cohort #3 in Phase 1b. Therefore,
      activities for the planned Phase 2 were not initiated.

      This decision to stop further development of this combination was taken due to the challenge
      for enrollment in this very rare patient population along with the rapidly evolving disease
      landscape setting.
    

Trial Arms

NameTypeDescriptionInterventions
INC280 single agentExperimental
  • INC280 single agent
INC280 in combination with erlotinibExperimental
  • INC280 in combination with erlotinib
Platinum in combination with pemetrexedActive ComparatorPlatinum (cisplatin or carboplatin) in combination with pemetrexed
  • Platinum/pemetrexed

Eligibility Criteria

        Inclusion Criteria:

          -  Locally advanced or metastatic NSCLC

          -  EGFR mutation (L858R and /or ex19del)

          -  cMET amplification by FISH (GCN ≥ 6),

          -  Acquired resistance to EGFR TKI (1st or 2nd génération)

          -  ECOG performance status (PS) ≤ 1.

        Exclusion Criteria:

          -  Prior treatment with 3rd generation TKI

          -  PhaseII : Prior treatment with any of the following agents:

               -  Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor.

               -  Concomitant EGFR TKI and platinum based chemotherapy as first line regimen.

               -  Platinum-based chemotherapy as first line treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination
Time Frame:First 28 days of dosing
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Phase Ib: Progression Free Survival (PFS)
Time Frame:Every 6 weeks, up to 2 years
Safety Issue:
Description:Correlation between IHC determined expression level and PFS
Measure:Phase Ib: Overall Survival (OS)
Time Frame:Every 3 weeks, up to 5 years
Safety Issue:
Description:OS, defined as time from the first dose of study treatment to death due to any cause
Measure:Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability
Time Frame:Every 3 weeks, up to 2 years
Safety Issue:
Description:Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).
Measure:Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters
Time Frame:6 weeks
Safety Issue:
Description:Composite pharmacokinetics of INC280 in the presence of erlotinib.
Measure:Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280
Time Frame:6 weeks
Safety Issue:
Description:Composite pharmacokinetics of erlotinib in the presence of INC280.
Measure:Phase Ib: Disease Control Rate (DCR)
Time Frame:Every 6 weeks, up to 2 years
Safety Issue:
Description:DCR, proportion of patients with best overall response of CR, PR or SD
Measure:Phase Ib: Duration of Response (DOR)
Time Frame:Every 6 weeks, up to 2 years
Safety Issue:
Description:DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause
Measure:Phase Ib: Progression-free Survival (PFS)
Time Frame:Every 6 weeks, up to 2 years
Safety Issue:
Description:PFS, defined as time from the first dose of study treatment to disease progression or death due to any cause
Measure:Phase Ib: Number of patients with serious adverse events as a measure of safety and tolerability
Time Frame:Every 3 weeks, up to 2 years
Safety Issue:
Description:Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Non-Small Cell Lung Cancer
  • NSCLC
  • INC280
  • erlotinib
  • advanced/metastatic non-small cell lung cancer
  • EGFR mutation
  • cMET amplification
  • EGFR tyrosine kinase inhibitor (EGFR TKI)

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