The purpose of this study is to evaluate the safety and efficacy of dabrafenib in combination with trametinib in Chinese patients with BRAF V600E mutation-positive metastatic Non-Small Cell Lung Cancer. The general study design has been discussed and agreed with Chinese Health Authority and is applying a similar design used for global pivotal phase II study (BRF113928).
Name: Dabrafenib
Name: Trametinib
Description: Overall Response Rate is defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) by central independent review as per RECIST v1.1 criteria
Measure: Overall Response Rate (ORR), central independent review assessed by RECIST v1.1 Time: From baseline until disease progression, death, lost to follow-up or withdrawal of consent, whichever occurs first, assessed up to approximately 12 months from treatment initiationDescription: ORR is defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) by investigator assessment as per RECIST 1.1 criteria
Measure: Overall response rate (ORR), investigator assessed by RECIST v1.1 Time: From baseline until disease progression, death, lost to follow-up or withdrawal of consent, whichever occurs first, assessed up to approximately 12 months from treatment initiationDescription: PFS is defined as the interval between first dose and the earliest date of disease progression or death due to any cause. PFS will be assessed via local review according to RECIST 1.1.
Measure: Progression Free Survival (PFS), investigator assessed by RECIST v1.1 Time: From baseline until disease progression or death due to any cause, whichever occurs first, assessed up to approximately 12 months from treatment initiationDescription: DoR is defined for the subset of subjects with confirmed CR or PR, as the time from first documented evidence of CR or PR until time of first documented disease progression according to RECIST v1.1 per local review or death due to any cause
Measure: Duration of Response (DoR), investigator assessed by RECIST v1.1 Time: From first documented response until first documented progression or death due to any cause, whichever occurs first, assessed up to approximately 12 months from treatment initiationDescription: OS is defined as the time from first dose until death due to any cause
Measure: Overall Survival (OS) Time: From baseline until death due to any cause, assessed up to approximately 33 months from treatment initiationDescription: Mean trough concentration will be calculated at each timepoint
Measure: Trough concentration of dabrafenib Time: Pre-dose sample at visits week 3, 6 and 12Description: Mean trough concentration will be calculated at each timepoint
Measure: Trough concentration of dabrafenib metabolites Time: Pre-dose sample at visits week 3, 6 and 12Description: Mean trough concentration will be calculated at each timepoint
Measure: Trough concentration of trametinib Time: Pre-dose sample at visits week 3, 6 and 12Description: EQ-5D-5L is a standardized measure to assess the overall health-related quality of life in patients.
Measure: Mean change from baseline in the European Quality of Life (EuroQol)- 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) score Time: From baseline, every 3 weeks until end of treatment (up to approximately 32 months after treatment initiation)Description: EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients.
Measure: Mean change from baseline in the European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) score Time: From baseline, every 3 weeks until end of treatment (up to approximately 32 months after treatment initiation)Description: EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire.
Measure: Mean Change from Baseline in the European Organization for Research and Treatment of Cancer lung cancer specific module (EORTC QLQ-LC13) score Time: From baseline, every 3 weeks until end of treatment (up to approximately 32 months after treatment initiation)Description: Safety profile of dobrafenib in combination with trametinib. Incidence of Adverse Events and Serious Adverse events, including abnormal laboratory values or test results.
Measure: Number of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs) Time: From baseline until end of study, assessed up to approximately 33 months from treatment initiationAllocation: N/A
Single Group Assignment
There is one SNP
An Open-Label, Single-arm Study to Evaluate the Safety and Efficacy of Dabrafenib in Combination With Trametinib in Chinese Patients With BRAF V600E Mutation-Positive Metastatic Non-Small Cell Lung Cancer. --- V600E ---
A Study of Dabrafenib in Combination With Trametinib in Chinese Patients With BRAF V600E Mutant Metastatic NSCLC The purpose of this study is to evaluate the safety and efficacy of dabrafenib in combination with trametinib in Chinese patients with BRAF V600E mutation-positive metastatic Non-Small Cell Lung Cancer. --- V600E ---
A Study of Dabrafenib in Combination With Trametinib in Chinese Patients With BRAF V600E Mutant Metastatic NSCLC The purpose of this study is to evaluate the safety and efficacy of dabrafenib in combination with trametinib in Chinese patients with BRAF V600E mutation-positive metastatic Non-Small Cell Lung Cancer. --- V600E --- --- V600E ---
Incidence of Adverse Events and Serious Adverse events, including abnormal laboratory values or test results.. Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (according to AJCC 8th edition) that is BRAF V600E mutation-positive by local test result from a qualified assay (NMPA and/or MOH-approved) - Previously treated or untreated for metastatic NSCLC: 1. Subjects previously treated should have received no more than 3 prior systemic therapies for metastatic disease, including one prior platinum based chemotherapy, and should have documented disease progression on a prior treatment regimen (i.e. --- V600E ---
The amount of time a patient must use a condom for 16 weeks post treatment discontinuation - Subjects with active Hepatitis B infection (HbsAg positive) - Subjects with positive test for hepatitis C ribonucleic acid (HCV RNA) - Concurrent participation in other clinical trials using experimental therapies Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (according to AJCC 8th edition) that is BRAF V600E mutation-positive by local test result from a qualified assay (NMPA and/or MOH-approved) - Previously treated or untreated for metastatic NSCLC: 1. Subjects previously treated should have received no more than 3 prior systemic therapies for metastatic disease, including one prior platinum based chemotherapy, and should have documented disease progression on a prior treatment regimen (i.e. --- V600E ---
The amount of time a patient must use a condom for 16 weeks post treatment discontinuation - Subjects with active Hepatitis B infection (HbsAg positive) - Subjects with positive test for hepatitis C ribonucleic acid (HCV RNA) - Concurrent participation in other clinical trials using experimental therapies Carcinoma, Non-Small-Cell Lung Carcinoma, Non-Small-Cell Lung This is a single arm, open label, multicenter phase II study evaluating the efficacy and safety of dabrafenib in combination with trametinib in Chinese subjects with BRAF V600E mutation positive AJCC v8 stage IV Non-Small Cell Lung Cancer. --- V600E ---
Subjects with stage IV BRAF V600E mutant Non-Small Cell Lung Cancer confirmed by local qualified assay (approved by China health authorities) will be enrolled in this study. --- V600E ---
Central confirmation testing for BRAF V600E will be performed. --- V600E ---