A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors

Completed · Phase 1/Phase 2

Conditions studied: Solid Tumors Harboring a BRAF V600 Mutation

In brief

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.

Key facts

Study ID

NCT01543698

Run by

Pfizer

People needed

189

Starts

2012-05-28

Expected to finish

2023-03-09

Last updated by the study team

2024-03-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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

Where it is running

• H. Lee Moffitt Cancer Center & Research Institute, Inc. — Tampa, Florida, United States
• Moffitt McKinley Outpatient Center — Tampa, Florida, United States
• Johns Hopkins Sidney Kimmel Comprehensive Cancer Center — Baltimore, Maryland, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Ophthalmic Consultants of Boston Inc (OCB) — Boston, Massachusetts, United States
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States
• Chris O'Brien Lifehouse Hospital — Camperdown, New South Wales, Australia
• Melanoma Institute Australia — North Sydney, New South Wales, Australia
• Westmead Hospital-Redbank Rd — Northmead, New South Wales, Australia
• Westmead Hospital-Redbank Rd — Westmead, New South Wales, Australia
• Westmead Hospital — Westmead, New South Wales, Australia
• Melanoma Institute Australia — North Sydney, Australia
• UZ Leuven- Gasthuisberg Campus — Leuven, Vlaams Brabant, Belgium
• Sir Mortimer B. Davis-Jewish General Hospital — Montreal, Quebec, Canada
• Hôpital Saint louis — Paris, France
• Service de radiologie - Hopital Saint Louis — Paris, France
• Azienda Ospedaliera Monaldi — Naples, Campania, Italy
• Azienda Ospedaliera Universitaria Federico II — Naples, Campania, Italy
• IRCCS Fondazione Pascale — Naples, Campania, Italy
• ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda — Milan, Italy
• Istituto Nazionale per lo studio e la cura dei tumori Fondazione Giovanni Pascale — Naples, Italy
• National Cancer Centre Singapore — Singapore, Singapore
• Hospital Universitario Vall d'Hebrón - PPDS — Barcelona, Spain
• Hospital Universitario HM Sanchinarro ? CIOCC — Madrid, Spain
• University Hospital Zürich, Dermatology — Zurich-Airport, Canton of Zurich, Switzerland

Full record on ClinicalTrials.gov

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