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

Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03240393
• Other study ID #: CINC280A2202
• Status: Withdrawn
• Phase: Phase 2
• Start date: July 31, 2018
• Est. completion date: October 26, 2021

Study information

• Verified date: July 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 26, 2021
• Est. primary completion date: October 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small-Cell Lung Cancer

Intervention

Drug:
• INC280
cMET GCN = 6 cMET GCN = 4 and < 6 cMET mutations

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Outcome

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