<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04452877</url>
  </required_header>
  <id_info>
    <org_study_id>CDRB436ECN01</org_study_id>
    <nct_id>NCT04452877</nct_id>
  </id_info>
  <brief_title>A Study of Dabrafenib in Combination With Trametinib in Chinese Patients With BRAF V600E Mutant Metastatic NSCLC</brief_title>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and efficacy of dabrafenib in combination&#xD;
      with trametinib in Chinese patients with BRAF V600E mutation-positive metastatic Non-Small&#xD;
      Cell Lung Cancer. The general study design has been discussed and agreed with Chinese Health&#xD;
      Authority and is applying a similar design used for global pivotal phase II study&#xD;
      (BRF113928).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single arm, open label, multicenter phase II study evaluating the efficacy and&#xD;
      safety of dabrafenib in combination with trametinib in Chinese participant with BRAF V600E&#xD;
      mutation positive AJCC v8 stage IV Non-Small Cell Lung Cancer.&#xD;
&#xD;
      Participants with stage IV BRAF V600E mutant Non-Small Cell Lung Cancer confirmed by local&#xD;
      qualified assay (approved by China health authorities) will be enrolled in this study.&#xD;
      Central confirmation testing for BRAF V600E will be performed. This study will enroll&#xD;
      participants:&#xD;
&#xD;
        1. who have not received any prior systemic anti-cancer therapy for metastatic disease&#xD;
           (i.e. dabrafenib/trametinib will be the 1st line treatment for metastatic disease)&#xD;
&#xD;
        2. who have relapsed or progressed on at least one prior platinum based chemotherapy prior&#xD;
           to enrollment but cannot have received more than 3 prior systemic therapies for&#xD;
           metastatic disease (i.e. dabrafenib/trametinib will be no less than second line&#xD;
           treatment for metastatic disease).&#xD;
&#xD;
      All participants must not have been previously exposed to a BRAF or MEK inhibitor.&#xD;
      Participants will receive the recommended dose of both drugs (dabrafenib 150 mg twice daily&#xD;
      and trametinib 2 mg once daily).&#xD;
&#xD;
      The primary endpoint for the study is Overall Response Rate, as determined by central&#xD;
      independent review, using Response Evaluation Criteria in Solid Tumors (RECIST v1.1).&#xD;
&#xD;
      Approximately 40 Chinese patients over 18 years old will be enrolled in this study and will&#xD;
      receive dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) combination therapy&#xD;
      until disease progression by RECIST 1.1, unacceptable toxicity, start of a new antineoplastic&#xD;
      therapy, pregnancy, withdrawal of consent, lost to follow-up, physician's decision, death, or&#xD;
      if study is terminated by the sponsor. Doses of study treatment may be modified and/or&#xD;
      interrupted for management of toxicities associated with study treatment.&#xD;
&#xD;
      Treatment beyond disease progression per RECIST is allowed if protocol specific criteria are&#xD;
      met. The tumor assessments will be performed every 6 weeks until Week 36, and every 12 weeks&#xD;
      thereafter until disease progression, death, lost of follow-up, or withdrawal of consent.&#xD;
      Survival and new anti-cancer therapy follow-up will continue until study completion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 19, 2020</start_date>
  <completion_date type="Anticipated">November 21, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 21, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate (ORR), central independent review assessed by RECIST v1.1</measure>
    <time_frame>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 initiation</time_frame>
    <description>Overall Response Rate is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) by central independent review as per RECIST v1.1 criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR), investigator assessed by RECIST v1.1</measure>
    <time_frame>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 initiation</time_frame>
    <description>ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) by investigator assessment as per RECIST 1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS), investigator assessed by RECIST v1.1</measure>
    <time_frame>From baseline until disease progression or death due to any cause, whichever occurs first, assessed up to approximately 12 months from treatment initiation</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR), investigator assessed by RECIST v1.1</measure>
    <time_frame>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 initiation</time_frame>
    <description>DoR is defined for the subset of participants 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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From baseline until death due to any cause, assessed up to approximately 33 months from treatment initiation</time_frame>
    <description>OS is defined as the time from first dose until death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough concentration of dabrafenib</measure>
    <time_frame>Pre-dose sample at visits week 3, 6 and 12</time_frame>
    <description>Mean trough concentration will be calculated at each timepoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough concentration of dabrafenib metabolites (hydroxy-dabrafenib, and desmethyl-dabrafenib)</measure>
    <time_frame>Pre-dose sample at visits week 3, 6 and 12</time_frame>
    <description>Mean trough concentration will be calculated at each timepoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough concentration of trametinib</measure>
    <time_frame>Pre-dose sample at visits week 3, 6 and 12</time_frame>
    <description>Mean trough concentration will be calculated at each timepoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change from baseline in the European Quality of Life (EuroQol)- 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) score</measure>
    <time_frame>From baseline, every 3 weeks until end of treatment (up to approximately 32 months after treatment initiation)</time_frame>
    <description>EQ-5D-5L is a standardized measure to assess the overall health-related quality of life in patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change from baseline in the European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) score</measure>
    <time_frame>From baseline, every 3 weeks until end of treatment (up to approximately 32 months after treatment initiation)</time_frame>
    <description>EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change from Baseline in the European Organization for Research and Treatment of Cancer lung cancer specific module (EORTC QLQ-LC13) score</measure>
    <time_frame>From baseline, every 3 weeks until end of treatment (up to approximately 32 months after treatment initiation)</time_frame>
    <description>EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From baseline until end of study, assessed up to approximately 33 months from treatment initiation</time_frame>
    <description>Safety profile of dabrafenib in combination with trametinib. Incidence of Adverse Events and Serious Adverse events, including abnormal laboratory values or test results.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Carcinoma, Non-Small-Cell Lung</condition>
  <arm_group>
    <arm_group_label>Dabrafenib in combination with trametinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dabrafenib 150 mg twice daily, trametinib 2 mg once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dabrafenib</intervention_name>
    <description>Dabrafenib will be provided by the sponsor to the investigative site or supplied locally as commercially available. Dabrafenib will be administered orally twice daily (150 mg BID) for Days 1-21 of a 21-day cycle.</description>
    <arm_group_label>Dabrafenib in combination with trametinib</arm_group_label>
    <other_name>DRB436</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trametinib</intervention_name>
    <description>Trametinib will be provided by the sponsor to the investigative site or supplied locally as commercially available. Trametinib will be administered orally once daily (2 mg QD) for Days 1-21 of a 21-day cycle</description>
    <arm_group_label>Dabrafenib in combination with trametinib</arm_group_label>
    <other_name>TMT212</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (according to&#xD;
             AJCC 8th edition) that is BRAF V600E mutation-positive by local test result from a&#xD;
             qualified assay (NMPA and/or MOH-approved)&#xD;
&#xD;
          -  Previously treated or untreated for metastatic NSCLC:&#xD;
&#xD;
               1. Participants previously treated should have received no more than 3 prior&#xD;
                  systemic therapies for metastatic disease, with at least one prior platinum based&#xD;
                  chemotherapy, and should have documented disease progression on a prior treatment&#xD;
                  regimen (i.e. RECIST 1.1)&#xD;
&#xD;
               2. Participants who have received prior therapy with checkpoint inhibitor therapy&#xD;
                  (i.e. anti-PD-1/PD-L1) must have had objective evidence of disease progression&#xD;
                  (i.e. RECIST v1.1) while on or after this therapy prior to enrollment.&#xD;
&#xD;
               3. Participants with EGFR or ALK mutation who have previously received therapy with&#xD;
                  EGFR or ALK inhibitor(s) respectively are eligible&#xD;
&#xD;
          -  Measurable disease per RECIST v1.1&#xD;
&#xD;
          -  Anticipated life expectancy of at least 3 months&#xD;
&#xD;
          -  ECOG performance status ≤ 2.&#xD;
&#xD;
          -  Adequate bone marrow and organ function as defined by the following laboratory values&#xD;
             without continuous supportive treatment (such as blood transfusion, coagulation&#xD;
             factors and/or platelet infusion, or red/white blood cell growth factor&#xD;
             administration) as assessed by local laboratory for eligibility: Hemoglobin ≥ 9 g/dL;&#xD;
             Absolute neutrophil count ≥ 1.5 × 109/L; Platelets ≥ 100 × 109/L; PT/INR and PTT ≤ 1.5&#xD;
             x ULN; Serum creatinine &lt; 1.5 mg/dL; Total bilirubin ≤ 1.5 × ULN (upper limit of&#xD;
             normal) except for participantss with Gilbert's syndrome who may only be included if&#xD;
             the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5&#xD;
             × ULN, except for participant with liver metastasis, who may only be included if&#xD;
             AST/ALT ≤ 5.0 × ULN Albumin ≥ 2.5 g/dL&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN)&#xD;
             as assessed by ECHO or MUGA scan&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with brain or leptomeningeal metastases are excluded if their these&#xD;
             metastases are: symptomatic or treated but not clinically and radiographically stable&#xD;
             3 weeks after local therapy or asymptomatic and untreated but &gt;1 cm in the longest&#xD;
             dimension&#xD;
&#xD;
          -  Previous treatment with a BRAF inhibitor or a MEK inhibitor&#xD;
&#xD;
          -  All prior anti-cancer treatment-related toxicities must be Grade 2 or less according&#xD;
             to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.03;&#xD;
             NCI, 2009) at the time of enrollment&#xD;
&#xD;
          -  Prior anti-cancer treatment within the last 2 weeks, and prior treatment with immune&#xD;
             checkpoint inhibitors within 4 weeks preceding the first dose of the study treatment.&#xD;
&#xD;
          -  Current use of a prohibited medication&#xD;
&#xD;
          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs&#xD;
             chemically related to the study treatments, their excipients, and/or dimethyl&#xD;
             sulfoxide (DMSO).&#xD;
&#xD;
          -  Participants with known history for testing positive for Human Immunodeficiency Virus&#xD;
             (HIV)&#xD;
&#xD;
          -  History of another malignancy &lt;3 years prior to starting study treatment or any&#xD;
             malignancy with confirmed activating RAS-mutation.&#xD;
&#xD;
          -  Cardiac or cardiac repolarization abnormality&#xD;
&#xD;
          -  A history or current evidence/risk of retinal vein occlusion (RVO) or serous&#xD;
             retinopathy&#xD;
&#xD;
          -  History or current interstitial lung disease or non-infectious pneumonitis&#xD;
&#xD;
          -  Any serious or unstable pre-existing medical conditions (aside from malignancy&#xD;
             exceptions specified above), psychiatric disorders, or other conditions that, in the&#xD;
             opinion of the investigator, could interfere with the participant's safety, obtaining&#xD;
             informed consent, or compliance with study procedures&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women.&#xD;
&#xD;
          -  Sexually active males (including those that have had a vasectomy) must use a condom&#xD;
             during intercourse and should not father a child during this period. The amount of&#xD;
             time a patient must use a condom for 16 weeks post treatment discontinuation&#xD;
&#xD;
          -  Participants with active Hepatitis B infection (HbsAg positive)&#xD;
&#xD;
          -  Participants with positive test for hepatitis C ribonucleic acid (HCV RNA)&#xD;
&#xD;
          -  Concurrent participation in other clinical trials using experimental therapies&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Harbin</city>
        <state>Heilongjiang</state>
        <zip>150081</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100036</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Changsha</city>
        <zip>410013</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Guangzhou</city>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>September 5, 2023</last_update_submitted>
  <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metastatic Non-Small Cell Lung Cancer</keyword>
  <keyword>NSCLC</keyword>
  <keyword>Chinese patients</keyword>
  <keyword>dabrafenib</keyword>
  <keyword>trametinib</keyword>
  <keyword>BRAF V600E</keyword>
  <keyword>treatment naive</keyword>
  <keyword>pre-treated</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trametinib</mesh_term>
    <mesh_term>Dabrafenib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04452877
org study id: CDRB436ECN01
nct id: NCT04452877
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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).
This is a single arm, open label, multicenter phase II study evaluating the efficacy and
      safety of dabrafenib in combination with trametinib in Chinese participant with BRAF V600E
      mutation positive AJCC v8 stage IV Non-Small Cell Lung Cancer.

      Participants 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.
      Central confirmation testing for BRAF V600E will be performed. This study will enroll
      participants:

        1. who have not received any prior systemic anti-cancer therapy for metastatic disease
           (i.e. dabrafenib/trametinib will be the 1st line treatment for metastatic disease)

        2. who have relapsed or progressed on at least one prior platinum based chemotherapy prior
           to enrollment but cannot have received more than 3 prior systemic therapies for
           metastatic disease (i.e. dabrafenib/trametinib will be no less than second line
           treatment for metastatic disease).

      All participants must not have been previously exposed to a BRAF or MEK inhibitor.
      Participants will receive the recommended dose of both drugs (dabrafenib 150 mg twice daily
      and trametinib 2 mg once daily).

      The primary endpoint for the study is Overall Response Rate, as determined by central
      independent review, using Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

      Approximately 40 Chinese patients over 18 years old will be enrolled in this study and will
      receive dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) combination therapy
      until disease progression by RECIST 1.1, unacceptable toxicity, start of a new antineoplastic
      therapy, pregnancy, withdrawal of consent, lost to follow-up, physician's decision, death, or
      if study is terminated by the sponsor. Doses of study treatment may be modified and/or
      interrupted for management of toxicities associated with study treatment.

      Treatment beyond disease progression per RECIST is allowed if protocol specific criteria are
      met. The tumor assessments will be performed every 6 weeks until Week 36, and every 12 weeks
      thereafter until disease progression, death, lost of follow-up, or withdrawal of consent.
      Survival and new anti-cancer therapy follow-up will continue until study completion.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR), central independent review assessed by RECIST v1.1
time frame: 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 initiation
description: Overall Response Rate is defined as the percentage of participants 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), investigator assessed by RECIST v1.1
time frame: 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 initiation
description: ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) by investigator assessment as per RECIST 1.1 criteria
measure: Progression Free Survival (PFS), investigator assessed by RECIST v1.1
time frame: From baseline until disease progression or death due to any cause, whichever occurs first, assessed up to approximately 12 months from treatment initiation
description: 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: Duration of Response (DoR), investigator assessed by RECIST v1.1
time frame: 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 initiation
description: DoR is defined for the subset of participants 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: Overall Survival (OS)
time frame: From baseline until death due to any cause, assessed up to approximately 33 months from treatment initiation
description: OS is defined as the time from first dose until death due to any cause
measure: Trough concentration of dabrafenib
time frame: Pre-dose sample at visits week 3, 6 and 12
description: Mean trough concentration will be calculated at each timepoint
measure: Trough concentration of dabrafenib metabolites (hydroxy-dabrafenib, and desmethyl-dabrafenib)
time frame: Pre-dose sample at visits week 3, 6 and 12
description: Mean trough concentration will be calculated at each timepoint
measure: Trough concentration of trametinib
time frame: Pre-dose sample at visits week 3, 6 and 12
description: Mean trough concentration will be calculated at each timepoint
measure: Mean change from baseline in the European Quality of Life (EuroQol)- 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) score
time frame: From baseline, every 3 weeks until end of treatment (up to approximately 32 months after treatment initiation)
description: 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 Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) score
time frame: 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 lung cancer specific module (EORTC QLQ-LC13) score
time frame: 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: Number of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: From baseline until end of study, assessed up to approximately 33 months from treatment initiation
description: Safety profile of dabrafenib in combination with trametinib. Incidence of Adverse Events and Serious Adverse events, including abnormal laboratory values or test results.
arm group label: Dabrafenib in combination with trametinib
arm group type: Experimental
description: Dabrafenib 150 mg twice daily, trametinib 2 mg once daily
intervention type: Drug
intervention name: Dabrafenib
description: Dabrafenib will be provided by the sponsor to the investigative site or supplied locally as commercially available. Dabrafenib will be administered orally twice daily (150 mg BID) for Days 1-21 of a 21-day cycle.
arm group label: Dabrafenib in combination with trametinib
other name: DRB436
intervention type: Drug
intervention name: Trametinib
description: Trametinib will be provided by the sponsor to the investigative site or supplied locally as commercially available. Trametinib will be administered orally once daily (2 mg QD) for Days 1-21 of a 21-day cycle
arm group label: Dabrafenib in combination with trametinib
other name: TMT212
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Trametinib
mesh term: Dabrafenib
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com