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

Phase 1TerminatedNCT02468661

Novartis Pharmaceuticals23 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non-Small Cell Lung Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (32)

Los Angeles Hematology/Oncology Medical Group

Los Angeles, California, United States

University of California Irvine Medical Center Chao Family SC

Orange, California, United States

Henry Ford Hospital SC

Detroit, Michigan, United States

Dartmouth Hitchcock Medical Center SC

Lebanon, New Hampshire, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Outcomes

Primary Outcomes

Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination

To determine MTD and/or RP2D of INC280 in combination with erlotinib

Time frame: First 28 days of dosing

Secondary Outcomes

Phase Ib: Overall response rate (ORR)

ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR)

Time frame: Every 3 weeks, up to 5 years

Phase Ib: Disease Control Rate (DCR)

DCR, proportion of patients with best overall response of CR, PR or SD

Time frame: Every 6 weeks, up to 2 years

Phase Ib: Duration of Response (DOR)

DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause

Time frame: Every 6 weeks, up to 2 years

Phase Ib: Progression-free Survival (PFS)

PFS, defined as time from the first dose of study treatment to disease progression or death due to any cause

Time frame: Every 6 weeks, up to 2 years

Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability

Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).

Time frame: Every 3 weeks, up to 2 years

Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters

Composite pharmacokinetics of INC280 in the presence of erlotinib.

Time frame: 6 weeks

Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280

Composite pharmacokinetics of erlotinib in the presence of INC280.

Time frame: 6 weeks