LGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma

Completed · Phase 2

Conditions studied: Melanoma

In brief

The primary purpose of this study is to assess the anti-tumor activity of LGX818/MEK162 in combination with targeted agents after progression on LGX818/MEK162 combination therapy, as well as the safety and tolerability of the novel triple combinations.

Key facts

Study ID

NCT02159066

Run by

Pfizer

People needed

158

Starts

2014-07-23

Expected to finish

2023-01-10

Last updated by the study team

2024-03-05

Who can join

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

You may qualify if…

• 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. PRINCIPAL EXCLUSION CRITERIA 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.
• Patients who have developed brain metastases during Part I of the study may continue to Part II upon discussion with Novartis 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. Patients with brain metastasis are not eligible for the combination with LEE011.
• 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 < 50% as determined by MUGA scan or ECHO
• History or presence of clinically significant ventricular arrhythmias or atrial fibrillation
• Clinically significant resting bradycardia
• Unstable angina pectoris ≤ 3 months prior to starting study drug
• Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug,
• QTcF > 480 msec. Patients with any of the following laboratory values at
• Screening/baseline:
• Absolute neutrophil count (ANC) <1,500/mm3 [1.5 x 109/L]
• Platelets < 100,000/mm3 [100 x 109/L]
• Hemoglobin < 9.0 g/dL
• Serum creatinine >1.5 x ULN or calculated or directly measured CrCl < 50% LLN (lower limit of normal)
• Serum total bilirubin >1.5 x ULN

Where it is running

• University of California Los Angeles — Los Angeles, California, United States
• Cancer Care Center — Los Angeles, California, United States
• Doris Stein Research Center Building — Los Angeles, California, United States
• Ronald Reagan UCLA Medical Center Drug Information Center Department of Pharmaceutical Services — Los Angeles, California, United States
• UCLA Dermatology Clinic — Los Angeles, California, United States
• UCLA Oncology Center — Los Angeles, California, United States
• UCLA Radiology — Los Angeles, California, United States
• Memorial Sloan Kettering Cancer Center Attn: Geny O'neill — New York, New York, United States
• Memorial Sloan Kettering Cancer Center Inpatient Hospital & Main Campus — New York, New York, United States
• Memorial Sloan Kettering Cancer Center- Outpatient Clinic — New York, New York, United States
• OHSU Knight Cancer Institute — Portland, Oregon, United States
• OHSU Center for Health and Healing 2 — Portland, Oregon, United States
• OHSU Center for Health and Healing — Portland, Oregon, United States
• OHSU Research Pharmacy Services — Portland, Oregon, United States
• Oregon Health and Science University — Portland, Oregon, United States
• Sarah Cannon Research Institute — Nashville, Tennessee, United States
• Tennessee Oncology, PLLC — Nashville, Tennessee, United States
• Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia
• East St Kilda Eye Clinic — Melbourne, Victoria, Australia
• Princess Margaret Cancer Center — Toronto, Ontario, Canada
• Sir Mortimer B. Davis-Jewish General Hospital — Monteral, Quebec, Canada
• University Clinic Heidelberg PPDS — Heidelberg, Baden-Wurttemberg, Germany
• Universitätsklinikum Würzburg — Würzburg, Bavaria, Germany
• Uniklinik Köln — Cologne, Germany
• Städtisches Klinikum München — München, Germany

Full record on ClinicalTrials.gov

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