unresectable or metastatic BRAF V600 mutant melanoma MedDRA version: 21.1 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
Conditions
Sponsors
Array BioPharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosis of locally advanced, unresectable or metastatic cutaneous 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 untreated central nervous system (CNS lesion) • Mucosal or uveal melanoma • History of leptomeningeal metastases • History of 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 hyper coagulability syndromes); • Patients with washout period < 6 weeks from the last dose of ipilimumab or other immunotherapy • Any previous systemic 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 or gastrointestinal disease • 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 Combo 450 (LGX818 450mg QD plus MEK162 45mg BID) prolongs progression free survival (PFS) compared with vemurafenib in patients with BRAF V600 mutant locally advanced unresectable or metastatic melanoma.;Secondary Objective: Key Part 1: 1) Determine the contribution of MEK162 to the combination using PFS comparison of Combo 450 vs LGX818 Key part 2: 2) Further quantify the contribution of MEK162 to the combination using PFS comparison of Combo 300 vs LGX818 Other part specific -Compare/estimate the effect of (3) Combo 450 vs vemurafenib/(4) Combo 450 vs. LGX818 in overall survival (OS) in Part 1 -Estimate the safety and tolerability of (5) Combo 450 and LGX818 in part1, (6) Combo 300 vs. LGX818, (7) Combo 300 vs. Combo 450 in Part2 -Estimate the effect of (8) Combo 300 vs. LGX818 in OS in Part2 -Estimate the effect in PFS and OS of (9) Combo 300 vs. vemurafenib and (10) Combo 300 vs. Combo 450 in Part2 Other Part1 and 2 -Estimate (11) the effect of LGX818 vs. vemurafenibin PFS and OS (Refer to Pg 61, Section 3 of Protocol for full text);Primary end point(s): Progression free survival: 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): - Overall Survival: time from the date of randomization to date of death due to any cause - Safety and tolerability: Adverse events and serious adverse events, changes in laboratory values, vital signs , ECGs, MUGA/echocardiogram and assessment of physical, dermatological and ocular examinations graded according to the NCI CTCAE v4.03 - Objective response rate: proportion of patient with a best overall response of complete response (CR) or partial response (PR). ORR will be calculated for confirmed and uncomfirmed responses separately. -Time to objective response: the time from date of randomization until first documented CR or PR. -Disease control rate: proportion of patient with a best overall response of CR, PR or stable disease (SD) -Duration of response: time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer -Time to definitive 10% deterioration in the FACT-M melanoma subscale and global health status score of the EORTC QLQ-C30. -Change from baseline in the FACT-M melanoma subscale, EQ-5D-5L, global health status score of the EORTC QLQ-C30 other EORTC QLQ-C30 subscales. - Time to definitive 1 point deterioration in ECOG PS Change from baseline in ECOG PS -Plasma concentration-profiles of LGX818 and MEK162 and model based PK parameters ;Timepoint(s) of evaluation of this end point: Key part 1 1) about 2 years Key Part 2 2) about 3 years Other part specific -(3), (4) about 5.5. years -(5) about 2 years -(6), (7) about 3 years -(8) about 5.5. years -(9) about 3 for PFS and 5.5. for OS -(10) about 3 for PFS and 5.5. years for OS Other Part 1 and 2 -(11) about 2, 3 and 5 years -(12), (13), (14), (15), (16), (17) about 2 (for Combo 450, LGX818 and vemurafenib evaluation) and 3 years (for Combo 300 evaluation) -(18) about 2 (for Combo 450 and LGX818 evaluation) and 3 years (for Combo 300 evaluation) | — |
Countries
Argentina, Australia, Brazil, Canada, China, Colombia, Czechia, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactAbdu Nessralla III
Array BioPharma Inc.
Outcome results
None listed