Efficacy and Safety of LGX818 in Patients With Advanced or Metastatic BRAF V600 Mutant NSCLC

Study Overview
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Brief Summary
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This is an open-label, multi-center, single arm phase II study to evaluate the efficacy and safety of novel BRAF (B-raf murine sarcoma viral oncogene homolog B1) inhibitor encorafenib (LGX818) when used as single agent in patients with advanced or metastatic (stage IIIB or IV) BRAF V600 mutant NSCLC. Patients must have progressed on or after at least one previous systemic, anti-cancer therapy for locally advanced or metastatic NSCLC.

Official Title
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A Phase II, Single Arm, Open-label, Multicenter, Study of Oral LGX818 in Patients With BRAF V600 Mutant, Advanced Non-small Cell Lung Cancer (NSCLC) That Have Progressed During or After at Least One Prior Chemotherapy

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: LGX818


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of BRAF V600E mutation in tumor tissue Histologically or cytologically confirmed diagnosis of Stage IIIB or IV NSCLC At least one measurable lesion as defined by RECIST v1.1 Patients must have progressed during or after at least one previous systemic, anti-cancer treatment for locally advanced or metastatic NSCLC. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status 0-2 Exclusion Criteria: Patients with symptomatic Central Nervous System (CNS) metastases History of leptomeningeal metastases Prior therapy with a BRAF inhibitor Patients taking prohibited medication listed in the protocol Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. Impaired cardiovascular function or clinically significant cardiovascular diseases Pregnant or lactating women or woman of childbearing potential

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LGX818<br>Adult patients, with confirmed diagnosis of BRAF V600E mutant advanced or metastatic NSCLC who have progressed on or after at least one prior systemic anticancer therapy. | Drug: LGX818<br>* Oral LGX818 300mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by investigator | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR per RECIST 1.1 as assessed by by Blinded independent review committee (BIRC) | baseline, every 6 weeks up to 24 weeks | 
| Progression-Free Survival (PFS) | PFS determined by investigator and BIRC. | baseline, every 6 weeks up to 24 weeks | 
| Duration of Response (DOR) | DOR by investigator and BIRC assessments. | baseline, every 6 weeks up to 24 weeks | 
| Overall survival (OS) | Overall survival (OS) | baseline, every 6 weeks up to 24 weeks | 
| Safety Profile | Adverse events and laboratory abnormalities | baseline, every 3 weeks up to 24 weeks | 
| Disease Control Rate (DCR) | DCR by investigator and BIRC assessments. | baseline, every 6 weeks up to 24 weeks | 
| Pharmacokinetics profile | Plasma concentration-time profiles of encorafenib (LGX818). | baseline, every 3 weeks up to 18 weeks | 
| Concordance between the BRAF mutation status from investigational diagnostic test and the companion diagnostic assay | Concordance rate between BRAF mutation status obtained using the investigational diagnostic test and the companion diagnostic assay which will be submitted for Pre-market approval (PMA) | screening, up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC,, Non-Small Cell Lung Cancer,, BRAF V600,, LGX818