This trial is active, not recruiting.

Condition solid tumors harboring a braf v600 mutation
Treatments lgx818, mek162, lee011
Phase phase 1/phase 2
Targets RAF, BRAF, MEK, CDK4, CDK6
Sponsor Array BioPharma
Start date May 2012
End date January 2018
Trial size 179 participants
Trial identifier NCT01543698, 2011-005875-17, CMEK162X2110


This is a multi-center, open-label, dose finding, Phase Ib dose escalation study to estimate the MTD(s) and/or RP2D(s) for the dual combination of LGX818 and MEK162 and the triple combination of LGX818 and MEK162 and LEE011, followed each independently by a Phase II part to assess the clinical efficacy and to further assess the safety of the combinations in selected patient populations. Oral LGX818 and MEK162 will be administered on a continuous schedule. Oral LEE011 will be administered once daily on a three weeks on, one week off schedule. Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. A cycle is defined as 28 days. The dose escalation parts of the trial will be conducted in adult patients with BRAF V600-dependent advanced solid tumors and is expected to enroll at least 18 patients for the dual combination and at least 12 patients for the triple combination. The dose escalation will be guided by a Bayesian logistic regression model (BLRM). Following MTD/RP2D declaration, patients will be enrolled in three Phase II arms for the dual combination and one Phase II arm for the triple combination. All patients will be followed for 30 days for safety assessments after study drugs discontinuation. All patients enrolled in the Phase II part of the study will be followed for survival.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
LGX818 QD and MEK162 BID
LGX818 QD and MEK162 BID and LEE011 QD 3 weeks on, 1 week off.

Primary Outcomes

Phase Ib: Estimation of Maximum Tolerated Dose (MTD) by measuring incidence of dose limiting toxicities (DLT)
time frame: up to 8 months
Phase II: Clinical efficacy
time frame: up to 14 months

Secondary Outcomes

Safety and tolerability of LGX818 and MEK162 dual combination, and LGX818 and MEK162 and LEE011 triple combination by evaluating the incidence and severity of adverse events (AE).
time frame: up to 17 months
Determination of single and multiple dose of Pharmacokinetics (PK) profile by measuring plasma concentrations versus time after study drug combination dosing (Phase Ib)
time frame: up to 8 months
Preliminary clinical anti-tumor activity by evaluating the objective response rate (Phase Ib)
time frame: up to 8 months
Further clinical efficacy (phase II)
time frame: up to 14 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or confirmed diagnosis of non-resectable advanced metastatic colorectal cancer (mCRC), or any other indication upon agreement with the Sponsor, whose disease has progressed despite previous antineoplastic therapy or for whom no further effective standard therapy is available - Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation - Evidence of measurable disease as determined by RECIST v1.1 - World Health Organization (WHO) Performance Status ≤ 2 - Negative serum pregnancy test within 72 hours prior to the first study dose in all women of childbearing potential Exclusion Criteria: Progressive disease following prior treatment with RAF-inhibitors in combination with MEK-inhibitors - Symptomatic or untreated leptomeningeal disease - Symptomatic brain metastases. Patients are not permitted to receive enzyme inducing anti-epileptic drugs - Known acute or chronic pancreatitis - History or current evidence of retinal disease, retinal vein occlusion or ophthalmopathy - Clinically significant cardiac disease - Patients with abnormal laboratory values at Screening/baseline - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818/MEK162 - Previous or concurrent malignancy - Pregnant or nursing (lactating) women - For addition of LEE011 in the triple combination, congenital long QT syndrome or family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ≥ 3, brain metastases at baseline, abnormal coagulation results PT/INR >1.5 x ULN or aPTT >1.5 x ULN. Other protocol-defined inclusion/exclusion criteria may apply

Additional Information

Official title A Phase Ib/II, Multicenter, Open-label, Dose Escalation Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF V600 - Dependent Advanced Solid Tumors
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Array BioPharma.
Location data was received from the National Cancer Institute and was last updated in May 2016.