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

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

ClinicalTrials.gov Identifier: NCT04452877

Novartis Reference Number: CDRB436ECN01

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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).

Condition 
Carcinoma, Non-Small-Cell Lung
Phase 
Phase 2
Overall status 
Recruiting
Enrollment count 
20 participants
Start date 
Aug 19, 2020
Completion date 
Jun 27, 2023
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Dabrafenib
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.
Drug
Trametinib
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

Eligibility Criteria

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:

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. RECIST 1.1)
Subjects 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.
Subjects 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 subjects 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 subjects 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

Exclusion Criteria:

Subjects 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).
Subjects 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 subject'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
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

Study Locations

China
Novartis Investigative Site
Recruiting
Harbin, 150081
Heilongjiang
China
Novartis Investigative Site
Recruiting
Jinan, 250117
Shandong
China
Novartis Investigative Site
Recruiting
Hangzhou, 310003
Zhejiang
China
Novartis Investigative Site
Recruiting
Hangzhou, 310022
Zhejiang
China
Novartis Investigative Site
Recruiting
Changsha, 410013
-
China
Novartis Investigative Site
Recruiting
Guangzhou, 510060
-
China
Novartis Investigative Site
Recruiting
Tianjin, 300052
-
China

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Name: 
Novartis Pharmaceuticals
Phone: 
Email: 

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Call 1-999-669-6682 or email [email protected]