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)
Overview
- Phase
- Phase 1
- Intervention
- INC280 single agent
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 23
- Locations
- 7
- Primary Endpoint
- Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
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.
Investigators
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
Arms & Interventions
INC280 200mg BID + ERL 150mg QD
Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
Intervention: INC280 single agent
INC280 200mg BID + ERL 150mg QD
Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
Intervention: erlotinib
INC280 400mg BID + ERL 150mg QD
Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
Intervention: INC280 single agent
INC280 400mg BID + ERL 150mg QD
Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
Intervention: erlotinib
Outcomes
Primary Outcomes
Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination
Time Frame: First 28 days of dosing
To determine MTD and/or RP2D of INC280 in combination with erlotinib
Secondary Outcomes
- Phase Ib: Duration of Response (DOR)(Every 6 weeks, up to 2 years)
- Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability(Every 3 weeks, up to 2 years)
- Phase Ib: Disease Control Rate (DCR)(Every 6 weeks, up to 2 years)
- Phase Ib: Overall response rate (ORR)(Every 3 weeks, up to 5 years)
- Phase Ib: Progression-free Survival (PFS)(Every 6 weeks, up to 2 years)
- Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters(6 weeks)
- Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280(6 weeks)