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
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Drug: INC280 single agent
- Registration Number
- NCT02468661
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 23
- 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.
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description INC280 200mg BID + ERL 150mg QD INC280 single agent Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD) INC280 400mg BID + ERL 150mg QD INC280 single agent Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD) INC280 400mg BID + ERL 150mg QD erlotinib Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD) INC280 200mg BID + ERL 150mg QD erlotinib Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
- Primary Outcome Measures
Name Time Method Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination First 28 days of dosing To determine MTD and/or RP2D of INC280 in combination with erlotinib
- Secondary Outcome Measures
Name Time Method Phase Ib: Duration of Response (DOR) 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
Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability 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).
Phase Ib: Disease Control Rate (DCR) Every 6 weeks, up to 2 years DCR, proportion of patients with best overall response of CR, PR or SD
Phase Ib: Overall response rate (ORR) Every 3 weeks, up to 5 years ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR)
Phase Ib: Progression-free Survival (PFS) 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
Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters 6 weeks Composite pharmacokinetics of INC280 in the presence of erlotinib.
Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280 6 weeks Composite pharmacokinetics of erlotinib in the presence of INC280.
Trial Locations
- Locations (7)
Henry Ford Hospital SC
🇺🇸Detroit, Michigan, 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
Novartis Investigative Site
🇪🇸Madrid, Spain
Dartmouth Hitchcock Medical Center SC
🇺🇸Lebanon, New Hampshire, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
NKI-AVL, Department of Thoracic-Oncology
🇳🇱Amsterdam, Netherlands