Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.

Phase 2TerminatedNCT01777776

Array BioPharma28 enrolled

Overview

To evaluate the safety, tolerability and efficacy of LEE011 and LGX818 when administered orally to patients with BRAF mutant melanoma.

In response to developments in the treatment of melanoma, the sponsor reviewed the data from the ongoing study and decided to halt further enrollment of patients in the Phase Ib part of the study. Consequently, the Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Locally Advanced Metastatic BRAF Mutant Melanoma

Interventions

LEE011DRUG

LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818DRUG

LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥18 years. * Diagnosis of locally advanced or metastatic melanoma along with written documentation of BRAF V600 mutation. * ECOG performance status of 0 - 2. * Patients enrolled into Phase Ib must have evidence of evaluable and/or measurable disease as determined by RECIST v1.1. * Patients enrolled into Phase II (BRAFi naïve and resistant) must have evidence of measurable disease as determined by RECIST v1.1. * Archival tumor tissue must be obtained for patients enrolled in Phase Ib and Phase II arm 1a/b- BRAFi naïve patients. If an archival tumor tissue is not available, a fresh tumor sample is acceptable. * For patients enrolled in the phase II arm 2, patients must agree to undergo a fresh tumor biopsy unless one was collected prior to study entry but at the time of disease relapse from the most recent BRAFi treatment. Exclusion Criteria: * Symptomatic brain metastases. * Symptomatic or untreated leptomeningeal disease. * Patients with inadequate laboratory values during screening. * In the phase II BRAFi naïve arms (1a/b), prior exposure to CDK4/6 inhibitor (e.g., PD 0332991) * Impaired cardiac function or clinically significant cardiac diseases. * Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of LEE011 or LGX818. * Patients with concurrent severe and/or uncontrolled concurrent medical conditions. * Previous or concurrent malignancy. * Major surgery \< 2 weeks before starting study treatment * Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C. Other protocol-defined inclusion/exclusion criteria may apply.

Locations (9)

University of Colorado Dept of Oncology

Aurora, Colorado, United States

Karmanos Cancer Institute Dept of Oncology

Detroit, Michigan, United States

Memorial Sloan Kettering Cancer Center Dept Oncology

New York, New York, United States

Outcomes

Primary Outcomes

Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1

Dose Limiting Toxicities (DLTs) during the first 28 days of the combination treatment of LEE011 and LGX818. Due to the halt of enrollment, no Maximum Tolerated Dose (MTD) was formally declared during the study.

Time frame: Cycle 1 (approximately 28 days)

Phase II - Progression Free Survival (PFS)

As per RECIST v1.1, PFS is the time from date of randomization/ start of treatment to the date of event defined as the first documented progression or death due to any cause. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed.

Time frame: Approximately 23 months after enrollment

Phase II - Objective Response Rate (ORR)

As per RECIST v1.1, ORR is defined as the proportion of patients with a best overall response of complete response or partial response. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed.

Time frame: Approximately 23 months after enrollment

Secondary Outcomes

Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE).

Time frame: Approximately 23 months after enrollment

Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE).

Time frame: Approximately 23 months after enrollment

Phase Ib/II - Plasma Concentration-time Profiles

Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to plasma concentration time profiles were not performed.

Time frame: 28-day cycles

Data from ClinicalTrials.gov

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