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.
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
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.
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.
Completion Date
Completion Date Type
Actual
Conditions
Non-Small Cell Lung Cancer
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
* 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
Inclusion 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.
* 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.
Gender
All
Gender Based
false
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)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02468661
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CINC280B2201
Overall Status
Terminated
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome Description
To determine MTD and/or RP2D of INC280 in combination with erlotinib
Outcome Measure
Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination
Outcome Time Frame
First 28 days of dosing
Secondary Ids
Secondary Id
2015-001241-84
Secondary Outcomes
Outcome Description
ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR)
Outcome Time Frame
Every 3 weeks, up to 5 years
Outcome Measure
Phase Ib: Overall response rate (ORR)
Outcome Description
DCR, proportion of patients with best overall response of CR, PR or SD
Outcome Time Frame
Every 6 weeks, up to 2 years
Outcome Measure
Phase Ib: Disease Control Rate (DCR)
Outcome Description
DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause
Outcome Time Frame
Every 6 weeks, up to 2 years
Outcome Measure
Phase Ib: Duration of Response (DOR)
Outcome Description
PFS, defined as time from the first dose of study treatment to disease progression or death due to any cause
Outcome Time Frame
Every 6 weeks, up to 2 years
Outcome Measure
Phase Ib: Progression-free Survival (PFS)
Outcome Description
Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).
Outcome Time Frame
Every 3 weeks, up to 2 years
Outcome Measure
Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability
Outcome Description
Composite pharmacokinetics of INC280 in the presence of erlotinib.
Outcome Time Frame
6 weeks
Outcome Measure
Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters
Outcome Description
Composite pharmacokinetics of erlotinib in the presence of INC280.
Outcome Time Frame
6 weeks
Outcome Measure
Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Phone
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
ERLOTINIB HYDROCHLORIDE
QUINAZOLINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS