The purpose of the study is to learn whether the study treatment (capmatinib), which already shows efficacy and safety in non-Chinese patients, could help Chinese patients with controlling their lung cancer in a safe way. Participants will have a type of lung cancer called non-small cell lung lancer (NSCLC), with a specific alteration in a part of their DNA (called mutation) of the MET gene, within a specific part of this gene called exon 14. Participants who have advanced (or metastatic) non-small cell lung cancer with specific mutations in the MET gene but without mutations in the EGFR or ALK genes, who are aged 18 years or older 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.
Name: Capmatinib
Description: ORR is defined as the proportion of participants with a best overall response (BOR) defined as complete response or partial response (CR+PR) by BIRC assessment per RECIST 1.1
Measure: Overall response rate (ORR) by blinded independent review committee (BIRC) assessment, by cohort Time: Up to approximately 23 monthsDescription: 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 participants with PR or CR
Measure: Duration of response (DOR) as assessed by BIRC, by cohort Time: From first documented response to first documented progression or death due to any cause, whichever comes first, assessed up to approximately 23 monthsDescription: ORR (CR+PR) and DOR per RECIST 1.1 by investigator assessment
Measure: Overall response rate (ORR) and duration of response (DOR) by investigator assessment, by cohort Time: Up to approximately 23 monthsDescription: TTR, calculated as the time from first dose of capmatinib to first documented response (CR+PR) for participants with PR or CR per RECIST 1.1 by BIRC and investigator
Measure: Time to response (TTR) by investigator and by BIRC assessment, by cohort Time: From first dose to first documented response of either CR or PR, assessed up to approximately 23 monthsDescription: DCR, calculated as the proportion of participants with BOR of CR, PR, or SD (stable disease) per RECIST 1.1 by BIRC and investigator
Measure: Disease Control Rate (DCR) by investigator and by BIRC assessment, by cohort Time: Up to approximately 23 monthsDescription: PFS, defined as time from first dose of capmatinib to progression or death due to any cause per RECIST 1.1 by BIRC and investigator
Measure: Progression Free Survival (PFS) by investigator and by BIRC assessment, by cohort Time: From first dose to the date of first documented progression or death from any cause, whichever comes first, assessed up to approximately 23 monthsDescription: OS is defined as the time from first dose to the date of death due to any cause.
Measure: Overall survival (OS) Time: From first dose to death due to any cause, assessed up to approximately 42 monthsDescription: Overall intracranial response rate (OIRR) calculated as the proportion of participants with a confirmed best overall intracranial response (BOIR) of CR or PR per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria as assessed by BIRC
Measure: Overall intracranial response rate (OIRR) Time: Up to approximately 23 monthsDescription: Intracranial disease control rate (IDCR), defined as the proportion of participants with a confirmed BOIR of CR or PR or SD (or non-CR/non-Progressive Disease) per RANO-BM criteria as assessed by BIRC review.
Measure: Intracranial disease control rate (IDCR) Time: Up to approximately 23 monthsDescription: Time to intracranial response (TTIR) defined as the time from the date of the start of study treatment to the date of the first documented intracranial response of either CR or PR per RANO-BM criteria as assessed by BIRC
Measure: Time to intracranial response (TTIR) Time: Up to approximately 23 monthsDescription: Duration of intracranial response (DOIR) defined as the time from the date of first documented intracranial response of either CR or PR to the date of the first documented intracranial progression per RANO-BM criteria as assessed by BIRC review or date of death due to any cause.
Measure: Duration of intracranial response (DOIR) Time: Up to approximately 23 monthsDescription: ORR, DOR and PFS per RECIST 1.1 for participants by MET mutation status assessed in circulating tumor DNA (ctDNA) at baseline, both by BIRC and investigator. The association between MET mutation status as measured in ctDNA at baseline with ORR, DOR and PFS will be established using Kaplan-Meier curve by cohort separately. Median survival together with their 95% confidence intervals will be reported.
Measure: Association between MET mutation status as measured in ctDNA at baseline with capmatinib efficacy Time: Up to approximately 23 monthsDescription: Steady state Ctrough and steady state 0.5- 1.5 hour and 3-5 hours post-dose concentrations
Measure: Plasma capmatinib concentration Time: Cycle 2 Day 1 pre-dose, 0.5-1.5 hours post-dose and 3-5 hours post dose and Cycle 3 Day 1 pre-dose. Each cycle duration is 21 daysDescription: 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 1 Day 1, Cycle 3 Day 1 and then every 6 weeks up to approximately 23 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 1 Day 1, Cycle 3 Day 1 and then every 6 weeks up to approximately 23 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 1 Day 1, Cycle 3 Day 1 and then every 6 weeks up to approximately 23 months. Each cycle duration is 21 days.Description: National Comprehensive Cancer Network Functional Assessment of Cancer Therapy (NCCN FACT) - Brain Symptom Index version 2.0 (FBrSI) symptom module, consisting of 24 items with a recall period of the past 7 days, will explore changes in symptoms associated with potential brain metastases.
Measure: Change from baseline in score as per NCCN FACT-Brain Symptom Index symptom module (FBrSI) questionnaire Time: Cycle 1 Day 1, Cycle 3 Day 1 and then every 6 weeks up to approximately 23 months. Each cycle duration is 21 days.Allocation: Non-Randomized
Single Group Assignment
There is one SNP
- Histologically or cytologically confirmed diagnosis of NSCLC that is: 1. EGFR wt: The EGFR wt status assessed as part of standard of care (EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations) 2. AND ALK rearrangement negative: assessed as part of standard of care by validated test 3. AND either: Cohort 1: Treatment naive participants with MET mutations, or Cohort 2: Pre-treated participants with MET mutations - Cohort 1: participants must not have received any systemic therapy for advanced/metastatic disease (stage IIIB, IIIC or IV NSCLC). --- L858R ---
Chinese adult participants with EGFR wild-type (wt) (EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations), anaplastic lymphoma kinase (ALK) rearrangement negative, advanced (stage IIIB, IIIC or IV) NSCLC disease harboring MET exon 14-skipping (METΔex14) mutations as determined by a Novartis central molecular laboratory will be treated in this study. --- L858R ---