unresectable or metastatic BRAF V600 mutant melanoma MedDRA version: 21.1 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Code: MEK162
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: MEK162
CAS Number: 606143-89-9
Current Sponsor code: MEK162
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
Array BioPharma Inc. (a wholly owned subsidiary of Pfizer Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma (AJCC Stage IIIB, IIIC, or IV) melanoma (AJCC Stage IIIB, IIIC, or IV) • Presence of BRAF V600E and/or V600K mutation in tumor tissue prior to randomization • Naïve untreated patients or patients who have progressed on or after prior first-line immunotherapy for unresectable locally advanced or metastatic melanoma; prior adjuvant therapy is permitted (e.g. IFN, IL-2 therapy, any other immunotherapy or radiotherapy), except the administration of BRAF or MEK inhibitors. • Evidence of at least one measurable lesion as detected by radiological or photographic methods • ECOG performance status of 0 or 1 • Adequate bone marrow, organ function, cardiac and laboratory parameters • Normal functioning of daily living activities Other protocol-defined inclusion criteria may apply 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 675 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 225
Exclusion criteria
Exclusion criteria: • Any active/non-stable brain lesion • Non-cutaneous melanoma • History of leptomeningeal metastases • History of or current evidence of retinal vein occlusion (RVO) • Patients with washout period < 12 weeks from the last dose of ipilimumab or other immunotherapy. • Any previous chemotherapy treatment, extensive radiotherapy or investigational agent other than immunotherapy, or patients who have received more than one line of immunotherapy for locally advanced unresectable or metastatic melanoma. • History of Gilbert's syndrome • Prior therapy with a BRAF inhibitor and/or a MEK- inhibitor • Impaired cardiovascular function or clinically significant cardiovascular diseases • Uncontrolled arterial hypertension despite medical treatment • HIV positive or active Hepatitis B, and/or active Hepatitis C • Impairment of gastrointestinal function • Patients with neuromuscular disorders that are associated with elevated CK. • Pregnant or nursing (lactating) women •Patients taking non-topical medication known to be a strong inhibitor of CYP3A4 • Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study Other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether treatment with LGX818 plus MEK162 prolongs progression free survival (PFS) compared with vemurafenib, and/or whether treatment with LGX818 prolongs PFS compared with vemurafenib in patients with BRAF V600 mutant locally advanced unresectable or metastatic melanoma.;Secondary Objective: Key secondary: To compare overall survival (OS) between study arms of LGX818 plus MEK162 and LGX818 versus vemurafenib. Other secondary: ? To estimate the treatment effect of LGX818 plus MEK162 versus LGX818 in terms of progression free survival (PFS) ? To assess objective response rate (ORR) by treatment arms ? To describe the time to objective response (TTR) ? To assess disease control rate (DCR) by treatment arms ? To evaluate duration of response (DOR) ? To determine the safety and tolerability of LGX818 plus MEK162 and LGX818 in this patient population ? To compare the patient-reported outcomes (PRO) between the treatment arms ? To compare the ECOG PS between the treatment arms ? To characterize the pharmacokinetics of LGX818 and MEK162 in this patient population ;Primary end point(s): Progression free survival for Combination versus vemurafenib and for LGX818 versus vemurafenib. PFS is defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever occurs first. PFS will be determined based on tumor assessment (RECIST version 1.1 criteria) as per Blinded Independent Review Committee (BIRC) and survival information. The local Investigator's assessments will be used as supportive analyses.;Timepoint(s) of evaluation of this end point: Approximately 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Key secondary: Overall Survival (OS), to compare OS between study arms of Combination and LGX818 versus vemurafenib. OS is calculated as the time from date of randomization to date of death due to any cause. 2. Progression free survival for Combination versus LGX818. PFS is defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever occurs first. PFS will be determined based on tumor assessment (RECIST version 1.1 criteria) as per Blinded Independent Review Committee (BIRC) and survival information. The local Investigator's assessments will be used as supportive analyses. 3. Overall Response Rate (ORR). ORR calculated as the proportion of patient with a best overall response of complete response (CR) or partial response (PR). ORR will be calculated for confirmed and unconfirmed responses separately. 4. Time to Objective Response (TTR). TTR calculated as the time from date of randomization until first documented complete response (CR) or partial response(PR). 5. Disease control rate (DCR). DCR calculated as the proportion of patient with a best overall response of CR, PR or stable disease (SD). 6. Duration of objective response (DOR). DOR calculated as the time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer 7. Safety and tolerability of Combination and LGX818. Number of patients with adverse events and serious adverse events , changes in laboratory values, vital signs, electrocardiograms (ECGs), MUGA(Multi Gated Acquisition Scan)/echocardiogram and assessment of physical,dermatological and ocular examinations graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 8. Time to definitive 10% deteriortaion in global health status (EORTC QLQC30) Time to definitive 10% deterioration in the global health status score of the EO | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Colombia, Czechia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Array BioPharma Inc. (a wholly owned subsidiary of Pfizer Inc.)
Outcome results
None listed