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

February 20, 2020 updated by: Novartis Pharmaceuticals

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)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The decision was taken to halt study enrollment with Cohort #3 in Phase Ib. Therefore, activities for the planned Phase II 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.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussel, Belgium, 1090
        • Novartis Investigative Site
      • Charleroi, Belgium, 6000
        • Novartis Investigative Site
  • France
      • Bordeaux, France, 33076
        • Novartis Investigative Site
      • Caen Cedex, France, 14021
        • Novartis Investigative Site
      • Marseille cedex 05, France, 13385
        • Novartis Investigative Site
      • Strasbourg Cedex, France, 67091
        • Novartis Investigative Site
    • Alpes Maritimes
      • Nice Cedex 2, Alpes Maritimes, France, 06189
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 13125
        • Novartis Investigative Site
    • Baden-Wuerttemberg
      • Tübingen, Baden-Wuerttemberg, Germany, 72076
        • Novartis Investigative Site
    • Bavaria
      • Regensburg, Bavaria, Germany, 93053
        • Novartis Investigative Site
  • Italy
    • BG
      • Bergamo, BG, Italy, 24127
        • Novartis Investigative Site
    • BS
      • Brescia, BS, Italy, 25123
        • Novartis Investigative Site
    • FC
      • Meldola, FC, Italy, 47014
        • Novartis Investigative Site
    • MI
      • Rozzano, MI, Italy, 20089
        • Novartis Investigative Site
    • PR
      • Parma, PR, Italy, 43100
        • Novartis Investigative Site
    • VR
      • Verona, VR, Italy, 37126
        • Novartis Investigative Site
  • Japan
    • Fukuoka
      • Fukuoka-city, Fukuoka, Japan, 811-1395
        • Novartis Investigative Site
    • Hyogo
      • Akashi, Hyogo, Japan, 673-8558
        • Novartis Investigative Site
    • Miyagi
      • Sendai city, Miyagi, Japan, 980 0873
        • Novartis Investigative Site
    • Okayama
      • Okayama-city, Okayama, Japan, 700-8558
        • Novartis Investigative Site
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Novartis Investigative Site
    • Korea
      • Seoul, Korea, Korea, Republic of, 05505
        • Novartis Investigative Site
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • NKI-AVL, Department of Thoracic-Oncology
  • Singapore
      • Singapore, Singapore, 169610
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28046
        • Novartis Investigative Site
    • Andalucia
      • Sevilla, Andalucia, Spain, 41013
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
  • United States
    • California
      • Los Angeles, California, United States, 90017
        • Los Angeles Hematology/Oncology Medical Group
      • Orange, California, United States, 92868
        • University of California Irvine Medical Center Chao Family SC
    • Michigan
      • Detroit, Michigan, United States, 48202-2689
        • Henry Ford Hospital SC
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center SC
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 generation)
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: INC280 200mg BID + ERL 150mg QD
Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
Drug: erlotinib
Drug: INC280 single agent
Experimental: INC280 400mg BID + ERL 150mg QD
Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
Drug: erlotinib
Drug: INC280 single agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination
Time Frame: First 28 days of dosing
To determine MTD and/or RP2D of INC280 in combination with erlotinib
First 28 days of dosing

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase Ib: Overall response rate (ORR)
Time Frame: Every 3 weeks, up to 5 years
ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR)
Every 3 weeks, up to 5 years
Phase Ib: Disease Control Rate (DCR)
Time Frame: Every 6 weeks, up to 2 years
DCR, proportion of patients with best overall response of CR, PR or SD
Every 6 weeks, up to 2 years
Phase Ib: Duration of Response (DOR)
Time Frame: Every 6 weeks, up to 2 years
DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause
Every 6 weeks, up to 2 years
Phase Ib: Progression-free Survival (PFS)
Time Frame: Every 6 weeks, up to 2 years
PFS, defined as time from the first dose of study treatment to disease progression or death due to any cause
Every 6 weeks, up to 2 years
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 and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).
Every 3 weeks, up to 2 years
Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters
Time Frame: 6 weeks
Composite pharmacokinetics of INC280 in the presence of erlotinib.
6 weeks
Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280
Time Frame: 6 weeks
Composite pharmacokinetics of erlotinib in the presence of INC280.
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2015

Primary Completion (Actual)

November 15, 2017

Study Completion (Actual)

December 5, 2018

Study Registration Dates

First Submitted

June 1, 2015

First Submitted That Met QC Criteria

June 8, 2015

First Posted (Estimate)

June 11, 2015

Study Record Updates

Last Update Posted (Actual)

February 24, 2020

Last Update Submitted That Met QC Criteria

February 20, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CINC280B2201
  • 2015-001241-84 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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