Non-small cell lung cancer MedDRA version: 18.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ C
Conditions
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Specific for Phase Ib: ? Patients must have received at least one line of systemic therapy, including one prior 1st generation (e.g., erlotinib, gefitinib) or 2nd generation (e.g., afatinib) EGFR TKI; any line of prior systemic chemotherapy is allowed ? Molecular pre-screening assessment: ? cMET-amplification (GCN ? 6) by FISH assessed from a biopsy or an archival tumor sample collected at or any time after the progression on prior 1st or 2nd generation EGFR TKI, determined locally or by a Novartis-designated central laboratory ? Patients with known EGFRT-790M mutation are not eligible ? Patients must have at the screening visit: Platelet count ? 75 x 109/L Specific for Phase II: ? Patients must have received one and only one prior line of 1st generation (e.g., erlotinib, gefitinib) or 2nd generation (e.g., afatinib) EGFR TKI for the treatment of locally advanced or metastatic NSCLC ? No prior chemotherapy is allowed, except: ? Patients, who switched from platinum-based chemotherapy to EGFR TKI during first line treatment within 28 days since the start date of chemotherapy, will be allowed to enter the study, in the absence of disease progression ? Prior neoadjuvant/adjuvant cytotoxic chemotherapy is not allowed, unless the relapse occurred more than 12 months after the last administration of neoadjuvant/adjuvant chemotherapy ? Molecular pre-screening assessment: ? cMET-amplification (GCN ? 6) by FISH determined by a Novartis-designated central laboratory on a newly obtained tumor biopsy (preferred) or an archival tumor sample obtained at or any time after the progression on prior 1st or 2nd generation EGFR TKI ? EGFR-T790M negative status assessed from a biopsy or an archival tumor sample collected at or any time after the progression on prior 1st or 2nd generation EGFR TKI, determined locally by either Roche Cobas or Qiagen therascreen test or by a Novartis designated central laboratory ? Presence of at least one measurable lesion according to RECIST v1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation. ? Patients must have at the screening visit: ? White blood cell count ? 4 x 109/L ? Platelet count ? 100 x 109/L Common for Phase Ib and Phase II: ? ? 18 years of age at the time of informed consent. ? Locally advanced or metastatic NSCLC (stage IIIB and is not a candidate for definitive multimodality therapy or IV) other than predominantly squamous cell histology harboring EGFR mutation known to be associated with EGFR TKI drug sensitivity (exon 19 deletion or L858R). ? Patients must meet the criteria for acquired resistance to EGFR TKI (either 1st generation (e.g., erlotinib, gefitinib) or 2nd generation (e.g., afatinib)) defined as: Documented clinical benefit (CR, PR, or SD (? 6 months) as per RECIST) or Demonstrated progression, while on continuous treatment, or within 30 days since the date of last administration of EGFR TKI, per RECIST ? Patients must have recovered from all toxicities related to prior anticancer therapies to grade ? 1 (CTCAE v 4.03). Patients with any grade of al
Exclusion criteria
Exclusion criteria: Specific Phase II: ? Patients with history of severe hypersensitivity reaction to platinum containing drugs, pemetrexed or any known excipients of these drugs. ? 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. Common for Phase Ib and Phase II: ? Prior treatment with any 3rd generation EGFR TKI (e.g., CO1686, AZD9192). ? Symptomatic central nervous system (CNS) metastases ? Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention). ? Presence of clinically significant ophthalmologic abnormalities ? Strong inhibitors or moderate inducers of CYP3A4; strong inducers of CYP3A4; strong inhibitors or strong inducers of CYP1A2; proton pump inhibitors, within 1 week prior to start of treatment with INC280 and for the duration of the study ? Pregnant or nursing women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Phase Ib: Frequency and characteristics of DLTs to the INC280 and erlotinib combination Phase II: PFS, defined as time from randomization to progression or death due to any cause, by investigator?s assessment according to RECIST v1.1 ;Timepoint(s) of evaluation of this end point: As defined per protocol; Main Objective: Phase Ib: To determine MTD and/or RP2D of INC280 in combination with erlotinib Phase II: To compare the antitumor activity of INC280 alone, and INC280 in combination with erlotinib, vs platinum with pemetrexed, as measured by Progression Free Survival (PFS) per investigator?s assessment ; Secondary Objective: Phase Ib: ? To assess the antitumor activity of INC280 in combination with erlotinib, as measured by overall response rate (ORR), disease control rate (DCR), duration of response (DOR) and PFS per investigator?s assessment ? To evaluate overall survival (OS) ? To determine safety and tolerability of INC280 in combination with erlotinib ? To characterize the PK of INC280 in the presence of erlotinib ? To characterize the PK of erlotinib in the presence of INC280 Phase II: ? To assess the antitumor activity of INC280 alone, and INC280 in combination with erlotinib, vs. platinum with pemetrexed, as measured by ORR, DCR, and DOR per Investigator?s assessment ? To evaluate OS ? To determine safety and tolerability of the combination of INC280 and erlotinib and of INC280 single agent ? To characterize the PK of INC280 in the presence of erlotinib ? To characterize the PK of INC280 single agent ? To characterize the PK of erlotinib in the presence of INC280 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase Ib: ? ORR, DCR, DOR, PFS by investigator?s assessment according to RECIST v1.1 ? OS ? Incidence of adverse events and serious adverse events, change in vital signs, laboratory results and ECG ? Plasma concentration-time profiles and pharmacokinetic parameters of INC280 and of erlotinib Phase II: ? ORR, DCR, DOR by investigator?s assessment according to RECIST v1.1 ? OS ? Incidence of adverse events and serious adverse events, change in vital signs, laboratory results and ECG ? Plasma concentrations of INC280 ? Plasma concentrations of erlotinib ;Timepoint(s) of evaluation of this end point: As defined per protocol | — |
Countries
Belgium, Brazil, Canada, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Netherlands, Portugal, Russian Federation, Singapore, Spain, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactDepartamento Médico Oncología (GMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed