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 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: CINC280B22012015-001241-84
• Study Type: interventional
• Target: 23
• Locations: 10 countries
• Sites: 32

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.

Conditions

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Phase Ib: Overall response rate (ORR)

  Every 3 weeks, up to 5 years

• Phase Ib: Disease Control Rate (DCR)

  Every 6 weeks, up to 2 years

• Phase Ib: Duration of Response (DOR)

  Every 6 weeks, up to 2 years

• Phase Ib: Progression-free Survival (PFS)

  Every 6 weeks, up to 2 years

• Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability

  Every 3 weeks, up to 2 years

Study Arms (2)

INC280 200mg BID + ERL 150mg QD

EXPERIMENTAL

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

Drug: INC280 single agent; Drug: erlotinib

INC280 400mg BID + ERL 150mg QD

EXPERIMENTAL

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

Drug: INC280 single agent; Drug: erlotinib

Interventions

INC280 single agent DRUG

INC280 200mg BID + ERL 150mg QD; INC280 400mg BID + ERL 150mg QD

erlotinib DRUG

INC280 200mg BID + ERL 150mg QD; INC280 400mg BID + ERL 150mg QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (32)

Los Angeles Hematology/Oncology Medical Group

Los Angeles, California, 90017, United States

Location

University of California Irvine Medical Center Chao Family SC

Orange, California, 92868, United States

Location

Henry Ford Hospital SC

Detroit, Michigan, 48202-2689, United States

Location

Dartmouth Hitchcock Medical Center SC

Lebanon, New Hampshire, 03756, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98105, United States

Location

Novartis Investigative Site

Brussels, 1090, Belgium

Location

Novartis Investigative Site

Charleroi, 6000, Belgium

Location

Novartis Investigative Site

Nice, Alpes Maritimes, 06189, France

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Caen, 14021, France

Location

Novartis Investigative Site

Marseille, 13385, France

Location

Novartis Investigative Site

Strasbourg, 67091, France

Location

Novartis Investigative Site

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

Location

Novartis Investigative Site

Berlin, 13125, Germany

Location

Novartis Investigative Site

Bergamo, BG, 24127, Italy

Location

Novartis Investigative Site

Brescia, BS, 25123, Italy

Location

Novartis Investigative Site

Meldola, FC, 47014, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Parma, PR, 43100, Italy

Location

Novartis Investigative Site

Verona, VR, 37126, Italy

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 811-1395, Japan

Location

Novartis Investigative Site

Akashi, Hyōgo, 673-8558, Japan

Location

Novartis Investigative Site

Sendai, Miyagi, 980 0873, Japan

Location

Novartis Investigative Site

Okayama, Okayama-ken, 700-8558, Japan

Location

NKI-AVL, Department of Thoracic-Oncology

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 1, 2015
• First Posted: June 11, 2015
• Study Start: September 23, 2015
• Primary Completion: November 15, 2017
• Study Completion: December 5, 2018
• Last Updated: February 24, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); FR (5); NL (1); SG (1); IT (6); DE (3); JP (4); ES (3); BE (2); KR (2)