The purpose of the study is to learn whether the study drug (capmatinib) helps to control lung cancer better compared to a single agent chemotherapy (docetaxel) and whether it is safe when given to patients suffering from a particular type of lung cancer. This type of cancer is called non-small cell lung cancer (NSCLC) with certain specific genetic alterations (called mutations) of a gene called MET, within a specific part of the gene called exon 14. Approximately 90 people with advanced or metastatic lung cancer, with these specific mutations in the MET gene but without changes in their epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genes, will be enrolled in this study. The study drug, capmatinib (also known as INC280), is an oral drug that is called a 'targeted' medicine, which means it targets particular processes that may not be working properly in cancer cells (called dysregulation). The dysregulation of the MET signaling in cancer cells of patients with NSCLC is believed to make the cancer worse. Capmatinib has been shown to selectively block the effects of the MET gene and therefore may help in keeping the disease under control, stopping cancer cells from growing. Docetaxel is a standard chemotherapy medicine commonly used to treat your type of lung cancer. This standard, anti-cancer medicine is a cytotoxic chemotherapy. The reason for this study is to find out if capmatinib can control lung cancer better. Patients will be randomly assigned to get either capmatinib or docetaxel in a 2 to 1 ratio: - Capmatinib: 2 out of 3 possibility or 66% chance of getting this treatment, - Docetaxel: 1 out of 3 possibility or 33% chance of getting this treatment. During treatment, visits will be scheduled every 21 days.
Name: Capmatinib
Name: Docetaxel
Description: Progression free survival is defined as the time from the date of randomization to the date of the first documented progression assessed by BIRC according to RECIST 1.1, or death due to any cause
Measure: Progression free survival (PFS) per blinded independent review committee (BIRC) using RECIST v1.1 Time: From randomization to the date of first documented progression or death from any cause, whichever comes first, assessed up to approximately 21 monthsDescription: Proportion of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR), assessed by BIRC according to RECIST 1.1.
Measure: Overall response (ORR) per RECIST 1.1 by BIRC Time: Up to approximately 21 monthsDescription: Proportion of participants with confirmed BOR of CR or PR, assessed by local review according to RECIST 1.1.
Measure: Overall response (ORR) per RECIST 1.1 by investigator Time: Up to approximately 21 monthsDescription: Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by BIRC according to RECIST 1.1.
Measure: Time to response (TTR) per RECIST 1.1 by BIRC Time: From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 monthsDescription: Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by local review according to RECIST 1.1.
Measure: Time to response (TTR) per RECIST 1.1 by investigator Time: From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 monthsDescription: Time from the date of first documented response (CR or PR) to the first documented progression by BIRC per RECIST 1.1 or death due to any cause.
Measure: Duration of response (DOR) per RECIST 1.1 by BIRC Time: From first documented response to first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 monthsDescription: Time from the date of first documented response (CR or PR) to the first documented progression by local review per RECIST 1.1 or death due to any cause.
Measure: Duration of response (DOR) per RECIST 1.1 by investigator Time: From first documented response to first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 monthsDescription: Proportion of participants with a BOR of confirmed CR, PR and stable disease (SD) assessed by BIRC according to RECIST 1.1
Measure: Disease Control Rate (DCR) per RECIST 1.1 by BIRC Time: Up to approximately 21 monthsDescription: Proportion of participants with a BOR of confirmed CR, PR and SD assessed by local review according to RECIST 1.1
Measure: Disease Control Rate (DCR) per RECIST 1.1 by investigator Time: Up to approximately 21 monthsDescription: Time from the date of randomization to the date of the first documented progression assessed by local review according to RECIST 1.1, or death due to any cause
Measure: Progression free survival (PFS) per investigator using RECIST v1.1 Time: From randomization to the date of first documented progression or death from any cause, whichever comes first, assessed up to approximately 21 monthsDescription: OS is defined as the time from the date of randomization to the date of death due to any cause.
Measure: Overall survival (OS) Time: From randomization to death due to any cause, assessed up to approximately 42 monthsDescription: Safety profile of capmatinib. Incidence of Adverse Events and Serious Adverse events, including abnormal laboratory values or test results.
Measure: Percentage of patients with Adverse Events and Serious Adverse events. Time: Up to approximately 42 monthsDescription: Plasma concentrations of capmatinib. Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Measure: Plasma capmatanib concentration Time: Cycle (C) 1 Day (D) 15 pre-dose, 1 and 4 hours post-dose, C3 D1 pre-dose. Each cycle duration is 21 days.Description: EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients.
Measure: Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Time: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months. Each cycle duration is 21 days.Description: EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire.
Measure: Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13) Time: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months. Each cycle duration is 21 days.Description: EQ-5D-5L is a standardized measure to assess the overall health-related quality of life in patients.
Measure: Change from baseline in score as per European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) questionnaire Time: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months. Each cycle duration is 21 days.Description: Proportion of participants with confirmed best overall intracranial response (BOIR) of CR or partial response (PR), as assessed by BIRC review per RANO-BM criteria.
Measure: Overall intracranial response rate (OIRR) Time: Up to approximately 21 monthsDescription: Time from date of first documented intracranial response (CR or PR) to first documented intracranial progression per RANO-BM or date of death due to underlying cause of cancer.
Measure: Duration of intracranial response (DOIR) Time: From date of first documented intracranial response (CR or PR) to first documented intracranial progression, assessed up to approximately 21 monthsDescription: Time from date of randomization to first documented intracranial response of either CR or PR, per RANO-BM criteria and assessed by BIRC, which must be subsequently confirmed.
Measure: Time to intracranial response (TTIR) Time: From date of randomization to first documented intracranial response of either CR or PR, assessed up to approximately 21 monthsDescription: Proportion of participants with a BOR of confirmed CR, PR and stable disease (SD) (or non-CR/non-PD) per RANO-BM, assessed by BIRC.
Measure: Intracranial disease control rate (IDCR) Time: Up to approximately 21 monthsAllocation: Randomized
Parallel Assignment
There is one SNP
The EGFR wt status (for EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations. --- L858R ---