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

NCT ID: NCT01543698

Last Updated: 2024-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 189 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-28
• Study Completion Date: 2023-03-09

Brief Summary

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.

Conditions

Solid Tumors Harboring a BRAF V600 Mutation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

dual combination

LGX818 QD and MEK162 BID

Group Type: EXPERIMENTAL

LGX818

Intervention Type: DRUG

MEK162

Intervention Type: DRUG

triple combination

LGX818 QD and MEK162 BID and LEE011 QD 3 weeks on, 1 week off.

Group Type: EXPERIMENTAL

LGX818

Intervention Type: DRUG

MEK162

Intervention Type: DRUG

LEE011

Intervention Type: DRUG

Interventions

LGX818

Intervention Type: DRUG

MEK162

Intervention Type: DRUG

LEE011

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Melanoma Institute Australia

North Sydney, , Australia

Service de radiologie - Hopital Saint Louis

Paris, , France

IRCCS Fondazione Pascale

Naples, Campania, Italy

Azienda Ospedaliera Monaldi

Napoli, Campania, Italy

UZ Leuven- Gasthuisberg Campus

Leuven, Vlaams Brabant, Belgium

Sir Mortimer B. Davis-Jewish General Hospital

Montreal, Quebec, Canada

Hôpital Saint louis

Paris, , France

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

Azienda Ospedaliera Universitaria Federico II

Napoli, 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

Napoli, , 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

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Countries

United States; Australia; Belgium; Canada; France; Italy; Singapore; Spain; Switzerland

References

Sullivan RJ, Weber J, Patel S, Dummer R, Carlino MS, Tan DSW, Lebbe C, Siena S, Elez E, Wollenberg L, Pickard MD, Sandor V, Ascierto PA. A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAFV600E/K -mutant Solid Tumors. Clin Cancer Res. 2020 Oct 1;26(19):5102-5112. doi: 10.1158/1078-0432.CCR-19-3550. Epub 2020 Jul 15.

Reference Type: DERIVED

PMID: 32669376 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

C4221005

Identifier Type: OTHER

Identifier Source: secondary_id

2011-005875-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CMEK162X2110

Identifier Type: -

Identifier Source: org_study_id