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

Phase 2

Withdrawn

• Conditions: Carcinoma; Non-Small-Cell Lung Cancer
• Interventions: Drug: INC280

• Registration Number: NCT03240393
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-07-26
• Study First Submitted QC: 2017-08-01
• Study First Posted: 2017-08-07
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-24
• Last Update Posted: 2018-07-26
• Study Start: 2018-07-31
• Primary Completion: 2021-10-26
• Study Completion: 2021-10-26

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
cMET GCN ≥ 6	INC280	Pre-treated patients with cMET GCN ≥ 6 treated with INC280 at 400mg BID
cMET GCN ≥ 4 and < 6	INC280	Pre-treated patients with cMET GCN ≥ 4 and \< 6 treated with INC280 at 400 mgBID
cMET mutations	INC280	Pre-treated patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID

Primary Outcome Measures

Name	Time	Method
ORR based on Central Radiology review/assessment (BIRC)	at least 18 weeks	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

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR) by investigator	at least 18 weeks	DOR per RECIST 1.1 by investigator assessment
ORR by Investigator	at least 18 weeks	ORR (complete response (CR)+ partial response (PR)) per RECIST 1.1 by investigator assessment
Disease Control Rate (DCR) by BIRC	at least 18 weeks	DCR per RECIST 1.1 by BIRC assessment
Progression-free Survival (PFS) by BIRC	at least 18 weeks	PFS per RECIST 1.1 by BIRC assessment
Progression-free Survival (PFS) by investigator	at least 18 weeks	PFS per RECIST 1.1 by investigator assessment
Overall Survival (OS)	at least 18 weeks	OS, defined as time from first dose of INC280 to death due to any cause
Cmax profile of INC280	6 weeks	Pharmacokinetics of INC280
Cmin profile of INC280	6 weeks	Pharmacokinetics of INC280
Duration of Response (DOR) by BIRC - Key Secondary	at least 18 weeks	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.
Cmax profile of INC280 metabolite CMN288	6 weeks	Pharmacokinetics of INC280 metabolite CMN288
Time to Response (TTR) by BIRC	at least 18 weeks	TTR per RECIST 1.1 by BIRC assessment
Time to Response (TTR) by investigator	at least 18 weeks	TTR per RECIST 1.1 by investigator assessment
Cmin profile of INC280 metabolite CMN288	6 weeks	Pharmacokinetics of INC280 metabolite CMN288
Disease Control Rate (DCR) by investigator	at least 18 weeks	DCR per RECIST 1.1 by investigator assessment
Plasma concentration-time profiles of INC280	6 weeks	Pharmacokinetics of INC280
Plasma concentration-time profiles of INC280 metabolite CMN288	6 weeks	Pharmacokinetics of INC280 metabolite CMN288