Non-Small Cell Lung Cancer
Conditions
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)
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.
Interventions
DRUGINC280 single agent
DRUGerlotinib
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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: 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: 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: 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. |
| 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). |
Countries
Belgium, France, Germany, Italy, Japan, Netherlands, Singapore, South Korea, Spain, United States
Outcome results
None listed