A Study of Dabrafenib in Combination With Trametinib in Chinese Patients With BRAF V600E Mutant Metastatic NSCLC

NCT04452877 | Completed Phase 2 Results

• 1 other identifier: CDRB436ECN01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 8

Brief Summary

This was a single-arm, open label, multicenter phase II, study of dabrafenib in combination with trametinib in Chinese participants with BRAF V600E mutation positive, stage IV NSCLC (American joint committee on cancer staging 8th edition). Approximately 40 Chinese adults were to be enrolled in this study. Participants were to be treated with dabrafenib in combination with trametinib until disease progression, start of a new anti-neoplastic therapy, unacceptable toxicity, pregnancy, withdrawal of consent, lost to follow-up, physician's decision, death, or if study be terminated by the sponsor. The general study design was discussed and agreed with China National Medical Products Administration and was based on a similar design used in the global pivotal phase II study (Study 113928 / NCT01336634).

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Metastatic Non-Small Cell Lung Cancer; NSCLC; Chinese patients; dabrafenib; trametinib; BRAF V600E; treatment naive; pre-treated

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR), Central Independent Review Assessed by RECIST v1.1

  Overall Response Rate (ORR) was defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per central independent review assessment and according to RECIST 1.1.

  From baseline until disease progression, death, lost to follow-up or withdrawal of consent, whichever occurs first, assessed up to approximately 50 months from treatment initiation

Secondary Outcomes (11)

• Overall Response Rate (ORR), Investigator Assessed by RECIST v1.1

  From baseline until disease progression, death, lost to follow-up or withdrawal of consent, whichever occurs first, assessed up to approximately 50 months from treatment initiation

• Progression Free Survival (PFS), Investigator Assessed by RECIST v1.1

  From baseline until disease progression or death due to any cause, whichever occurs first, assessed up to approximately 50 months from treatment initiation

• Duration of Response (DoR), Investigator Assessed by RECIST v1.1

  From first documented response until first documented progression or death due to any cause, whichever occurs first, assessed up to approximately 50 months from treatment initiation

• Overall Survival (OS)

  From baseline until death due to any cause, assessed up to approximately 50 months from treatment initiation

• Trough Concentration of Dabrafenib

  Pre-dose sample at visits week 3, 6 and 12

Study Arms (1)

Dabrafenib in combination with trametinib

EXPERIMENTAL

Dabrafenib 150 mg twice daily, trametinib 2 mg once daily

Drug: Dabrafenib; Drug: Trametinib

Interventions

Trametinib DRUG

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

Also known as: TMT212

Dabrafenib in combination with trametinib

Dabrafenib DRUG

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.

Also known as: DRB436

Dabrafenib in combination with trametinib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Participants previously treated should have received no more than 3 prior systemic therapies for metastatic disease, with at least one prior platinum based chemotherapy, and should have documented disease progression on a prior treatment regimen (i.e. RECIST 1.1)
• Participants who have received prior therapy with checkpoint inhibitor therapy (i.e. anti-PD-1/PD-L1) must have had objective evidence of disease progression (i.e. RECIST v1.1) while on or after this therapy prior to enrollment.
• Participants with EGFR or ALK mutation who have previously received therapy with EGFR or ALK inhibitor(s) respectively are eligible
• Measurable disease per RECIST v1.1
• Anticipated life expectancy of at least 3 months
• ECOG performance status ≤ 2.
• Adequate bone marrow and organ function as defined by the following laboratory values without continuous supportive treatment (such as blood transfusion, coagulation factors and/or platelet infusion, or red/white blood cell growth factor administration) as assessed by local laboratory for eligibility: Hemoglobin ≥ 9 g/dL; Absolute neutrophil count ≥ 1.5 × 109/L; Platelets ≥ 100 × 109/L; PT/INR and PTT ≤ 1.5 x ULN; Serum creatinine \< 1.5 mg/dL; Total bilirubin ≤ 1.5 × ULN (upper limit of normal) except for participants with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN, except for participant with liver metastasis, who may only be included if AST/ALT ≤ 5.0 × ULN Albumin ≥ 2.5 g/dL
• Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN) as assessed by ECHO or MUGA scan

You may not qualify if:

• Participants with brain or leptomeningeal metastases are excluded if their these metastases are: symptomatic or treated but not clinically and radiographically stable 3 weeks after local therapy or asymptomatic and untreated but \>1 cm in the longest dimension
• Previous treatment with a BRAF inhibitor or a MEK inhibitor
• All prior anti-cancer treatment-related toxicities must be Grade 2 or less according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.03; NCI, 2009) at the time of enrollment
• Prior anti-cancer treatment within the last 2 weeks, and prior treatment with immune checkpoint inhibitors within 4 weeks preceding the first dose of the study treatment.
• Current use of a prohibited medication
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).
• Participants with known history for testing positive for Human Immunodeficiency Virus (HIV)
• History of another malignancy \<3 years prior to starting study treatment or any malignancy with confirmed activating RAS-mutation.
• Cardiac or cardiac repolarization abnormality
• A history or current evidence/risk of retinal vein occlusion (RVO) or serous retinopathy
• History or current interstitial lung disease or non-infectious pneumonitis
• Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that, in the opinion of the investigator, could interfere with the participant's safety, obtaining informed consent, or compliance with study procedures
• Pregnant or nursing (lactating) women.
• Sexually active males (including those that have had a vasectomy) must use a condom during intercourse and should not father a child during this period. The amount of time a patient must use a condom for 16 weeks post treatment discontinuation
• Participants with active Hepatitis B infection (HbsAg positive)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Novartis Investigative Site

Harbin, Heilongjiang, 150081, China

Location

Novartis Investigative Site

Changsha, Hunan, 410013, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310003, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310022, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Guangzhou, 510060, China

Location

Novartis Investigative Site

Shanghai, 200032, China

Location

Related Publications (1)

• Fan Y, Zhou J, Zhao Y, Yu Y, Yang N, Li J, Wang J, Zhao J, Wang Z, Chen J, Zhu T, Li H, Passos VQ, Bury-Maynard D, Zhang L. Efficacy, safety, and quality of life of dabrafenib plus trametinib treatment in Chinese patients with BRAF V600E mutation-positive metastatic non-small cell lung cancer. Transl Lung Cancer Res. 2024 Dec 31;13(12):3382-3391. doi: 10.21037/tlcr-24-494. Epub 2024 Dec 27.

  PMID: 39830765 RESULT

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: July 1, 2020
• Study Start: August 19, 2020
• Primary Completion: November 7, 2024
• Study Completion: November 7, 2024
• Last Updated: January 13, 2026
• Results First Posted: November 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

CN (8)