Status:

COMPLETED

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

Lead Sponsor:

Novartis Pharmaceuticals

Conditions:

Carcinoma, Non-Small-Cell Lung

Eligibility:

All Genders

18-99 years

Phase:

PHASE2

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 co...

Eligibility Criteria

Inclusion

  • 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

Exclusion

  • 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)
  • Participants with positive test for hepatitis C ribonucleic acid (HCV RNA)
  • Concurrent participation in other clinical trials using experimental therapies

Key Trial Info

Start Date :

August 19 2020

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

November 7 2024

Estimated Enrollment :

40 Patients enrolled

Trial Details

Trial ID

NCT04452877

Start Date

August 19 2020

End Date

November 7 2024

Last Update

November 4 2025

Active Locations (8)

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Page 1 of 2 (8 locations)

1

Novartis Investigative Site

Harbin, Heilongjiang, China, 150081

2

Novartis Investigative Site

Changsha, Hunan, China, 410013

3

Novartis Investigative Site

Chengdu, Sichuan, China, 610041

4

Novartis Investigative Site

Hangzhou, Zhejiang, China, 310003