Study of Oral cMET Inhibitor INC280 in Chinese Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (NSCLC)

Phase II Multicenter 3-cohort Study of Oral cMET Inhibitor INC280 in Chinese Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (NSCLC) Who Have Received 1 or 2 Prior Lines of Systemic Therapy for Advanced/Metastatic Disease

A phase II study to evaluate antitumor activity of oral cMET inhibitor INC280 in adult Chinese patients with EGFR wild-type, advanced non-small cell lung cancer (NSCLC) who have received one or two prior lines of systemic therapy for advanced/metastatic disease as measured by overall response rate (ORR). The study will also evaluate safety and pharmacokinetics of INC280.

Study Overview

• Status: Withdrawn
• Conditions: Carcinoma; Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: INC280

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Stage IIIB or IV NSCLC (any histology) at the time of study entry

• Histologically or cytologically confirmed diagnosis of NSCLC that is:

  1. EGFR wt as per patient standard of care by a validated test
  2. AND ALK-negative rearrangement as part of the patient standard of care by a validated test

  3. AND (by central assessment) either:

     • Cohort 1: Pre-treated patients with cMET GCN ≥ 6 or
     • Cohort 2: Pre-treated patients with cMET GCN ≥4 and < 6, or
     • Cohort 3: Pre-treated patients with cMET mutations regardless of cMET GCN, or
• Patients must have failed one or two prior lines of systemic therapy for advanced/metastatic disease
• At least one measurable lesion as defined by RECIST 1.1
• Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.
• Patients must have adequate organ function
• ECOG performance status (PS) of 0 or 1

Details and other protocol-defined inclusion criteria may apply

Exclusion Criteria:

• Prior treatment with crizotinib, or any other cMET or HGF inhibitor
• Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations
• Patients with characterized ALK-positive rearrangement
• Clinically significant, uncontrolled heart diseases.

• Patients receiving treatment with medications that cannot be discontinued at least 1 week prior to first INC280 treatment and for the duration of the study:

  • Strong and moderate inhibitors of CYP3A4
  • Strong inducers of CYP3A4
• Impairment of GI function or GI disease that may significantly alter the absorption of INC280
• Patients receiving treatment with any enzyme-inducing anticonvulsant
• Previous anti-cancer and investigational agents within 4 weeks or ≤ 5 x half-life of the agent (whichever is longer) before first dose
• Pregnant or nursing women
• Women of child-bearing potential, unless they are using highly effective methods of contraception
• Sexually active males unless they use a condom during intercourse

Other protocol-defined exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cMET GCN ≥ 6; Pre-treated patients with cMET GCN ≥ 6 treated with INC280 at 400mg BID	Drug: INC280; cMET GCN ≥ 6 cMET GCN ≥ 4 and < 6 cMET mutations; Other Names: capmatinib
Experimental: cMET GCN ≥ 4 and < 6; Pre-treated patients with cMET GCN ≥ 4 and < 6 treated with INC280 at 400 mgBID	Drug: INC280; cMET GCN ≥ 6 cMET GCN ≥ 4 and < 6 cMET mutations; Other Names: capmatinib
Experimental: cMET mutations; Pre-treated patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID	Drug: INC280; cMET GCN ≥ 6 cMET GCN ≥ 4 and < 6 cMET mutations; Other Names: capmatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR based on Central Radiology review/assessment (BIRC)	Proportion of patients with a best overall response defined as complete response (CR) or partial response (PR) by Blinded Independent Review Committee (BIRC) assessment per RECIST 1.1	at least 18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS, defined as time from first dose of INC280 to death due to any cause	at least 18 weeks
Duration of Response (DOR) by BIRC - Key Secondary	Calculated as the time from the date of the first documented CR or PR by Blinded Independent Review Committee (BIRC) per RECIST 1.1 to the first documented progression or death due to any cause for patients with PR or CR.	at least 18 weeks
ORR by Investigator	ORR (complete response (CR)+ partial response (PR)) per RECIST 1.1 by investigator assessment	at least 18 weeks
Duration of Response (DOR) by investigator	DOR per RECIST 1.1 by investigator assessment	at least 18 weeks
Time to Response (TTR) by BIRC	TTR per RECIST 1.1 by BIRC assessment	at least 18 weeks
Time to Response (TTR) by investigator	TTR per RECIST 1.1 by investigator assessment	at least 18 weeks
Disease Control Rate (DCR) by BIRC	DCR per RECIST 1.1 by BIRC assessment	at least 18 weeks
Disease Control Rate (DCR) by investigator	DCR per RECIST 1.1 by investigator assessment	at least 18 weeks
Progression-free Survival (PFS) by BIRC	PFS per RECIST 1.1 by BIRC assessment	at least 18 weeks
Progression-free Survival (PFS) by investigator	PFS per RECIST 1.1 by investigator assessment	at least 18 weeks
Cmax profile of INC280	Pharmacokinetics of INC280	6 weeks
Cmax profile of INC280 metabolite CMN288	Pharmacokinetics of INC280 metabolite CMN288	6 weeks
Cmin profile of INC280	Pharmacokinetics of INC280	6 weeks
Cmin profile of INC280 metabolite CMN288	Pharmacokinetics of INC280 metabolite CMN288	6 weeks
Plasma concentration-time profiles of INC280	Pharmacokinetics of INC280	6 weeks
Plasma concentration-time profiles of INC280 metabolite CMN288	Pharmacokinetics of INC280 metabolite CMN288	6 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Anticipated): July 31, 2018
• Primary Completion (Anticipated): October 26, 2021
• Study Completion (Anticipated): October 26, 2021

Study Registration Dates

• First Submitted: July 26, 2017
• First Submitted That Met QC Criteria: August 1, 2017
• First Posted (Actual): August 7, 2017

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 24, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: NSCLC; MET; lung cancer; Non Small Cell Lung Cancer; Non-small cell lung cancer; INC280; MET amplification; MET mutation; lung adenocarcinoma; EGFR wild-type (wt); advanced non-small cell lung cancer; advanced/metastatic disease; Non-small cell lung carcinoma (NSCLC); treatment of lung cancer after first metastasis; Non small cell lung carcinoma; MET exon 14 deletion; MET exon 14 skipping; MET exon 14 mutation; MET inhibitor; MET dysregulation; MET activation; MET signaling; MET pathway; cMET
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma
• Other Study ID Numbers: CINC280A2202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Planned Shared Data Description: Copy and paste this Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No