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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

Primary Purpose

Non-Small Cell Lung Cancer

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
INC280 single agent
erlotinib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring 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)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Los Angeles Hematology/Oncology Medical Group
  • University of California Irvine Medical Center Chao Family SC
  • Henry Ford Hospital SC
  • Dartmouth Hitchcock Medical Center SC
  • Seattle Cancer Care Alliance
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • NKI-AVL, Department of Thoracic-Oncology
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

INC280 200mg BID + ERL 150mg QD

INC280 400mg BID + ERL 150mg QD

Arm Description

Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)

Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Phase Ib: Overall response rate (ORR)
ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR)
Phase Ib: Disease Control Rate (DCR)
DCR, proportion of patients with best overall response of CR, PR or SD
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
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
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).
Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters
Composite pharmacokinetics of INC280 in the presence of erlotinib.
Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280
Composite pharmacokinetics of erlotinib in the presence of INC280.

Full Information

First Posted
June 1, 2015
Last Updated
February 20, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02468661
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
Major challenge for enrollment of participants.
Study Start Date
September 23, 2015 (Actual)
Primary Completion Date
November 15, 2017 (Actual)
Study Completion Date
December 5, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
The study started as a single assignment study which was to move to a parallel design (3 arms) but the study was stopped after cohort #3 in the phase I part and so never moved into phase 2.
Masking
None (Open Label)
Masking Description
The study started as a non-randomized study, and was to move into randomized part in phase II. However the study was stopped after cohort #3 in the phase I part and so never moved into phase II.
Allocation
Non-Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
INC280 200mg BID + ERL 150mg QD
Arm Type
Experimental
Arm Description
Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
Arm Title
INC280 400mg BID + ERL 150mg QD
Arm Type
Experimental
Arm Description
Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
Intervention Type
Drug
Intervention Name(s)
INC280 single agent
Intervention Type
Drug
Intervention Name(s)
erlotinib
Primary Outcome Measure Information:
Title
Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination
Description
To determine MTD and/or RP2D of INC280 in combination with erlotinib
Time Frame
First 28 days of dosing
Secondary Outcome Measure Information:
Title
Phase Ib: Overall response rate (ORR)
Description
ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR)
Time Frame
Every 3 weeks, up to 5 years
Title
Phase Ib: Disease Control Rate (DCR)
Description
DCR, proportion of patients with best overall response of CR, PR or SD
Time Frame
Every 6 weeks, up to 2 years
Title
Phase Ib: Duration of Response (DOR)
Description
DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause
Time Frame
Every 6 weeks, up to 2 years
Title
Phase Ib: Progression-free Survival (PFS)
Description
PFS, defined as time from the first dose of study treatment to disease progression or death due to any cause
Time Frame
Every 6 weeks, up to 2 years
Title
Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability
Description
Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).
Time Frame
Every 3 weeks, up to 2 years
Title
Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters
Description
Composite pharmacokinetics of INC280 in the presence of erlotinib.
Time Frame
6 weeks
Title
Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280
Description
Composite pharmacokinetics of erlotinib in the presence of INC280.
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Los Angeles Hematology/Oncology Medical Group
City
Los Angeles
State/Province
California
ZIP/Postal Code
90017
Country
United States
Facility Name
University of California Irvine Medical Center Chao Family SC
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Henry Ford Hospital SC
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202-2689
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center SC
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Novartis Investigative Site
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Novartis Investigative Site
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Nice Cedex 2
State/Province
Alpes Maritimes
ZIP/Postal Code
06189
Country
France
Facility Name
Novartis Investigative Site
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Novartis Investigative Site
City
Caen Cedex
ZIP/Postal Code
14021
Country
France
Facility Name
Novartis Investigative Site
City
Marseille cedex 05
ZIP/Postal Code
13385
Country
France
Facility Name
Novartis Investigative Site
City
Strasbourg Cedex
ZIP/Postal Code
67091
Country
France
Facility Name
Novartis Investigative Site
City
Tübingen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
72076
Country
Germany
Facility Name
Novartis Investigative Site
City
Regensburg
State/Province
Bavaria
ZIP/Postal Code
93053
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Novartis Investigative Site
City
Bergamo
State/Province
BG
ZIP/Postal Code
24127
Country
Italy
Facility Name
Novartis Investigative Site
City
Brescia
State/Province
BS
ZIP/Postal Code
25123
Country
Italy
Facility Name
Novartis Investigative Site
City
Meldola
State/Province
FC
ZIP/Postal Code
47014
Country
Italy
Facility Name
Novartis Investigative Site
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Novartis Investigative Site
City
Parma
State/Province
PR
ZIP/Postal Code
43100
Country
Italy
Facility Name
Novartis Investigative Site
City
Verona
State/Province
VR
ZIP/Postal Code
37126
Country
Italy
Facility Name
Novartis Investigative Site
City
Fukuoka-city
State/Province
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Novartis Investigative Site
City
Akashi
State/Province
Hyogo
ZIP/Postal Code
673-8558
Country
Japan
Facility Name
Novartis Investigative Site
City
Sendai city
State/Province
Miyagi
ZIP/Postal Code
980 0873
Country
Japan
Facility Name
Novartis Investigative Site
City
Okayama-city
State/Province
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
NKI-AVL, Department of Thoracic-Oncology
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41013
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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