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

Sponsor

Array Biopharma, now a wholly owned subsidiary of Pfizer (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02109653

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: LGX818	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2015

Anticipated Primary Completion Date :

Nov 1, 2017

Anticipated Study Completion Date :

Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LGX818 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 Oral LGX818 300mg daily

Arm

Intervention/Treatment

Experimental: LGX818

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

Oral LGX818 300mg daily

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [up to 24 weeks]
ORR per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by investigator

Secondary Outcome Measures

Overall Response Rate (ORR) [baseline, every 6 weeks up to 24 weeks]
ORR per RECIST 1.1 as assessed by by Blinded independent review committee (BIRC)
Progression-Free Survival (PFS) [baseline, every 6 weeks up to 24 weeks]
PFS determined by investigator and BIRC.
Duration of Response (DOR) [baseline, every 6 weeks up to 24 weeks]
DOR by investigator and BIRC assessments.
Overall survival (OS) [baseline, every 6 weeks up to 24 weeks]
Overall survival (OS)
Safety Profile [baseline, every 3 weeks up to 24 weeks]
Adverse events and laboratory abnormalities
Disease Control Rate (DCR) [baseline, every 6 weeks up to 24 weeks]
DCR by investigator and BIRC assessments.
Pharmacokinetics profile [baseline, every 3 weeks up to 18 weeks]
Plasma concentration-time profiles of encorafenib (LGX818).
Concordance between the BRAF mutation status from investigational diagnostic test and the companion diagnostic assay [screening, up to 24 weeks]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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