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

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: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: erlotinib; Drug: INC280 single agent

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

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

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

How is the study designed?

Design Details

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

Number of Arms

2

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	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)	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)	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)	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)	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	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	Composite pharmacokinetics of INC280 in the presence of erlotinib.	6 weeks
Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280	Composite pharmacokinetics of erlotinib in the presence of INC280.	6 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

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: NSCLC; Non-Small Cell Lung Cancer; erlotinib; INC280; EGFR mutation; cMET amplification; advanced/metastatic non-small cell lung cancer; EGFR tyrosine kinase inhibitor (EGFR TKI)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• 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