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

Non-Small Cell Lung Cancer Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT02468661
• Other study ID #: CINC280B2201
• Secondary ID: 2015-001241-84
• Status: Terminated
• Phase: Phase 1
• Start date: September 23, 2015
• Est. completion date: December 5, 2018

Study information

• Verified date: February 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: December 5, 2018
• Est. primary completion date: November 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• INC280 single agent

• erlotinib

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Charleroi
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Caen Cedex
France	Novartis Investigative Site	Marseille cedex 05
France	Novartis Investigative Site	Nice Cedex 2	Alpes Maritimes
France	Novartis Investigative Site	Strasbourg Cedex
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Regensburg	Bavaria
Germany	Novartis Investigative Site	Tübingen	Baden-Wuerttemberg
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Meldola	FC
Italy	Novartis Investigative Site	Parma	PR
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Verona	VR
Japan	Novartis Investigative Site	Akashi	Hyogo
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Sendai city	Miyagi
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul
Netherlands	NKI-AVL, Department of Thoracic-Oncology	Amsterdam
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sevilla	Andalucia
United States	Henry Ford Hospital SC	Detroit	Michigan
United States	Dartmouth Hitchcock Medical Center SC	Lebanon	New Hampshire
United States	Los Angeles Hematology/Oncology Medical Group	Los Angeles	California
United States	University of California Irvine Medical Center Chao Family SC	Orange	California
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters	Composite pharmacokinetics of INC280 in the presence of erlotinib.	6 weeks
Secondary	Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280	Composite pharmacokinetics of erlotinib in the presence of INC280.	6 weeks

External Links

•   Novartis results database