Clinical trial NCT03240393: Study of Oral cMET Inhibitor INC280 in Chinese Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (NSCLC)
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Carcinoma
Non-Small-Cell Lung Cancer
Keywords: Non Small Cell Lung Cancer
NSCLC
INC280
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
lung cancer
lung adenocarcinoma
Non small cell lung carcinoma
Non-small cell lung cancer
MET exon 14 deletion
MET exon 14 skipping
MET exon 14 mutation
MET mutation
MET amplification
MET inhibitor
MET dysregulation
MET activation
MET signaling
MET pathway
MET
cMET
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-08-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: ORR based on Central Radiology review/assessment (BIRC)
timeFrame: at least 18 weeks
Secondary outcomes:
measure: Duration of Response (DOR) by BIRC - Key Secondary
timeFrame: at least 18 weeks
measure: ORR by Investigator
timeFrame: at least 18 weeks
measure: Duration of Response (DOR) by investigator
timeFrame: at least 18 weeks
measure: Time to Response (TTR) by BIRC
timeFrame: at least 18 weeks
measure: Time to Response (TTR) by investigator
timeFrame: at least 18 weeks
measure: Disease Control Rate (DCR) by BIRC
timeFrame: at least 18 weeks
measure: Disease Control Rate (DCR) by investigator
timeFrame: at least 18 weeks
measure: Progression-free Survival (PFS) by BIRC
timeFrame: at least 18 weeks
measure: Progression-free Survival (PFS) by investigator
timeFrame: at least 18 weeks
measure: Overall Survival (OS)
timeFrame: at least 18 weeks
measure: Cmax profile of INC280
timeFrame: 6 weeks
measure: Cmax profile of INC280 metabolite CMN288
timeFrame: 6 weeks
measure: Cmin profile of INC280
timeFrame: 6 weeks
measure: Cmin profile of INC280 metabolite CMN288
timeFrame: 6 weeks
measure: Plasma concentration-time profiles of INC280
timeFrame: 6 weeks
measure: Plasma concentration-time profiles of INC280 metabolite CMN288
timeFrame: 6 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: