Advanced non-small cell ling cancer MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age = 18 years 2. Stage IIIB or IV NSCLC (any histology) at the time of study entry 3.Histologically or cytologically confirmed diagnosis of NSCLC that is: a.EGFR wild-type. This should have been assessed as part of the patient standard of care by a validated test for EGFR mutations, as per the Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors (Lindeman et al 2013), b.AND ALK-negative rearrangement. This should have been assessed as part of the patient standard of care by a validated test, c.AND (as determined by central assessment at a Novartis designated laboratory) either: Cohort 1: Patients with cMET GCN = 6, including: Sub-cohort 1a: Patients with cMET GCN of =10, or Sub-cohort 1b: Patients with cMET GCN of = 6 and 9 g/dL; Calculated creatinine clearance (using Cockcroft-Gault formula) = 45 mL/min; Total bilirubin = 1.5 x ULN; Aspartate transaminase (AST) = 3 x ULN, except for patients with liver metastasis, who may only be included if AST = 5 x ULN; Alanine transaminase (ALT) = 3 x ULN, except for patients with liver metastasis, who may only be included if ALT = 5 x ULN; Alkaline phosphatase (ALP) = 5 x ULN; Asymptomatic serum amylase = grade 2. Patients with grade 1 or grade 2 serum amylase at the beginning of the study must be confirmed to have no signs and/or symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.); Serum lipase = ULN; Fasting plasma glucose = 175 mg/dL (= 9.7 mmol/L). Patients must have the following laboratory values within the laboratory normal limits or corrected to within normal limits with supplements during screening: Potassium; Magnesium; Phosphorus; Total calcium (corrected for serum albumin). ECOG performance status (PS) of 0 or 1. Please refer to protocol for further d
Exclusion criteria
Exclusion criteria: 1. Prior treatment with crizotinib, or any other cMET or HGF inhibitor 2. Patients with known hypersensitivity to any of the excipients of INC280 3. Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations. 4. Patients with characterized ALK-positive rearrangement 5. Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms 6. Presence or history of carcinomatous meningitis 7. Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type 8. Clinically significant, uncontrolled heart diseases. • Unstable angina within 6 months prior to screening • Myocardial infarction within 6 months prior to screening • History of documented congestive heart failure (New York Heart Association functional classification III-IV) • Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) = 160 mm Hg and/or Diastolic Blood Pressure (DBP) = 100 mm Hg, with or without antihypertensive medication. 9. Thoracic radiotherapy to lung fields = 4 weeks prior to starting INC280 or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy = 2 weeks prior to starting INC280 or patients who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions = 2 weeks prior to starting INC280 is allowed 10. Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior (2 weeks for resection of brain metastases) to starting INC280 or who have not recovered from side effects of such procedure. 11. Patients receiving treatment with medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with INC280 and for the duration of the study: • Strong inducers of CYP3A4 12. Impairment of GI function or GI disease that may significantly alter the absorption of INC280 13. Unable or unwilling to swallow tablets as per dosing schedule 14. Patients receiving unstable or increasing doses of corticosteroids. If patients are on corticosteroids for endocrine deficiencies or tumorassociated symptoms other than CNS related, dose must have been stabilized (or decreasing) for at least 5 days before first dose of INC280 15. Patients receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least 1 week before first dose of INC280, and for the duration of the study. Patients on nonenzyme- inducing anticonvulsants are eligible 16. For cohort 1 to 4 and cohort 6 Previous anti-cancer and investigational agents within 4 weeks or = 5 x half-life of the agent (whichever is longer) before first dose of INC280. If previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 4 weeks before first dose of INC280. If previous treatment is an oral targeted agent, then the treatment must be discontinued at least 5 x half-life of the agent before the first dos
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the antitumor activity of INC280, as measured by overall response rate (ORR) by Blinded Independent Review Committee (BIRC) assessment, by cohort/sub-cohort;Secondary Objective: To evaluate duration of response (DOR) as assessed by BIRC, by cohort/sub-cohort To evaluate ORR and DOR by investigator assessment, by cohort/sub-cohort To evaluate time to response (TTR), disease control rate (DCR) and progression-free survival (PFS) by investigator and by BIRC assessment, by cohort/sub-cohort To evaluate overall survival (OS), by cohort/sub-cohort To evaluate INC280 safety profile as monotherapy in NSCLC patients To characterize the pharmacokinetics of INC280 and metabolite CMN288;Primary end point(s): ORR, proportion of patients with a best overall response defined as complete response or partial response (CR+PR) by BIRC assessment per RECIST 1.1;Timepoint(s) of evaluation of this end point: as defined per protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. DOR, calculated as the time from the date of the first documented CR or PR by BIRC per RECIST 1.1 to the first documented progression or death due to any cause for patients with PR or CR 2. ORR (CR+PR) and DOR per RECIST 1.1 by investigator assessment 3. All calculated per RECIST 1.1, both by BIRC and investigator: • TTR, calculated as the time from first dose of INC280 to first documented response (CR+PR) for patients with PR or CR • DCR, calculated as the proportion of patients with best overall response of CR, PR, or SD • PFS, defined as time from first dose of INC280 to progression or death due to any cause 4. OS, defined as time from first dose of INC280 to death due to any cause 5. Incidence of adverse events and serious adverse events, change in vital signs, laboratory results (hematology, blood chemistry, and urinalysis) and ECG 6. Plasma concentration-time profiles and pharmacokinetic parameters estimated by non-compartmental analysis or population PK modeling;Timepoint(s) of evaluation of this end point: as defined per protocol | — |
Countries
Argentina, Austria, Belgium, Brazil, Canada, China, France, Germany, Israel, Italy, Japan, Korea, Republic of, Lebanon, Mexico, Netherlands, Norway, Poland, Russian Federation, Singapore, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactDrug Regulatory Affairs
Novartis Pharma GmbH
Outcome results
None listed