Locally Advanced or Metastatic BRAF V600 Melanoma
Conditions
Interventions
Product Name: encorafenib
Product Code: LGX818
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: encorafenib
Other descriptive name: LGX818
Concentration unit: mg milligram(s)
Concentration type
Sponsors
Array BioPharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients (males and females) Age = 18 years • Histologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IIIC to IV per American Joint Committee on Cancer [AJCC]) • Documented evidence of BRAF V600 mutation. • Newly obtained tumor biopsy at baseline, and patient agrees to a mandatory biopsy at the time of progression, if not medically contraindicated. • Evidence of measurable disease, as determined by RECIST v1.1. Inclusion criteria for triple combinations: Progressive disease following prior treatment with LGX818/MEK162 combination. A pre-LGX818/MEK162 combination archival tumor sample must be available Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 112 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: •Symptomatic or untreated leptomeningeal disease Symptomatic or untreated leptomeningeal disease. • Symptomatic brain metastases. Patients previously treated or untreated for brain metastases that are asymptomatic in the absence of corticosteroid therapy or on a stable dose of steroids for four weeks are allowed to enroll. Brain metastases must be stable at least 4 weeks with verification by imaging (e.g. brain MRI completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs. • Known acute or chronic pancreatitis. • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); • Clinically significant cardiac disease including any of the following: • CHF requiring treatment (NYH grade = 2), • LVEF 480 msec. Patients with any of the following laboratory values at Screening/baseline: • Absolute neutrophil count (ANC) 1.5 x ULN or calculated or directly measured CrCl 1.5 x ULN • AST/SGOT or ALT/SGPT > 2.5 x ULN, or > 5 x ULN if liver metastases are present Additional exclusion criteria for the triple combinations: Patients who have developed brain metastases during Part I of the study may continue to Part II upon discussion with Sponsor Medical Monitor. The brain metastasis must be either asymptomatic or treated and stable for at least 4 weeks and on a stable or tapering dose of steroids for at least 2 weeks. LGX818/MEK162/BKM120: • Patients with fasting glucose > 120 mg/dL or 6.7 mmol/L, and HbA1c > 8 %. • Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist: • Patient has a score = 12 on the PHQ-9 questionnaire • Patient has = CTCAE grade 3 anxiety LGX818/MEK162/BGJ398: • History and/or current evidence of significant ectopic mineralization/ calcification with the exception of calcified lymph nodes and asymptomatic vascular calcification. • Current evidence of corneal disorder/ keratopathy incl. but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivits etc., confirmed by ophthalmologic examination LGX818/MEK162/LEE011: • Patients with uncontrolled hypertension (please refer to WHO-ISH guidelines) are excluded from study. • QTcF >450 ms for males and >470 ms for females Congenital long QT syndrome or family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade = 3 and magnesium levels below the clinically relevant lower limits at study entry • Current evidence of brain metastasis or brain metastasis detected by mandatory CT/MRI at screening • PT/INR or aPTT > 1.5xULN • History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry. Documented ca
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the anti-tumor activity of LGX818/MEK162 in combination with targeted agents after progression on LGX818/MEK162 combination therapy;Secondary Objective: - To characterize the safety and tolerability of LGX818/MEK162 in combination with targeted agents - To estimate the MTD/RP2D of triple combinations after progression on LGX818/MEK162 therapy - To further assess anti-tumor activity of LGX818/MEK162 combination, and in combination with targeted agents after progression on LGX818/MEK162 combination - To characterize genomic alterations in tumor tissue at baseline and at tumor progression - To determine the PK profiles of LGX818, MEK162 and the third agents when given in combination and to assess drug-drug interaction ;Primary end point(s): Overall response rate ;Timepoint(s) of evaluation of this end point: 3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Incidence and severity of adverse events - Incidence rate of Dose Limiting Toxicities (DLTs) in Cycle 1 of Combination Part (Part II) - PFS, DOR, TTR, DCR and OS (Part II only) - Genomic alteration status(mutation/amplification/expression) of pre-defined markers - Plasma concentration and derived PK parameters of LGX818/MEK162 and targeted agents;Timepoint(s) of evaluation of this end point: - 3 years - 3 years - 3 years - 3 years - baseline, at progression with LGX818/MEK162 up to 3 years | — |
Countries
Australia, Canada, France, Germany, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactMargaret Vargo
Array BioPharma Inc.
Outcome results
None listed