Description:
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.
Title
- 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)
Clinical Trial IDs
- ORG STUDY ID:
CINC280B2201
- SECONDARY ID:
2015-001241-84
- NCT ID:
NCT02468661
Conditions
- Non-Small Cell Lung Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| INC280 single agent | | INC280 200mg BID + ERL 150mg QD |
| erlotinib | | INC280 200mg BID + ERL 150mg QD |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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) | - INC280 single agent
- 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) | - INC280 single agent
- erlotinib
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination |
| Time Frame: | First 28 days of dosing |
| Safety Issue: | |
| Description: | To determine MTD and/or RP2D of INC280 in combination with erlotinib |
Secondary Outcome Measures
| Measure: | Phase Ib: Overall response rate (ORR) |
| Time Frame: | Every 3 weeks, up to 5 years |
| Safety Issue: | |
| Description: | ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR) |
| Measure: | Phase Ib: Disease Control Rate (DCR) |
| Time Frame: | Every 6 weeks, up to 2 years |
| Safety Issue: | |
| Description: | DCR, proportion of patients with best overall response of CR, PR or SD |
| Measure: | Phase Ib: Duration of Response (DOR) |
| Time Frame: | Every 6 weeks, up to 2 years |
| Safety Issue: | |
| Description: | DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause |
| Measure: | Phase Ib: Progression-free Survival (PFS) |
| Time Frame: | Every 6 weeks, up to 2 years |
| Safety Issue: | |
| Description: | PFS, defined as time from the first dose of study treatment to disease progression or death due to any cause |
| Measure: | Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability |
| Time Frame: | Every 3 weeks, up to 2 years |
| Safety Issue: | |
| Description: | Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG). |
| Measure: | Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters |
| Time Frame: | 6 weeks |
| Safety Issue: | |
| Description: | Composite pharmacokinetics of INC280 in the presence of erlotinib. |
| Measure: | Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280 |
| Time Frame: | 6 weeks |
| Safety Issue: | |
| Description: | Composite pharmacokinetics of erlotinib in the presence of INC280. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial 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)
Last Updated
February 24, 2020
