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

NCT01777776 | Terminated Phase 1 Results

• 1 other identifier: CLEE011X2105
• Study Type: interventional
• Target: 28
• Locations: 4 countries
• Sites: 9

Brief Summary

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

Conditions

Locally Advanced Metastatic BRAF Mutant Melanoma

Keywords

Open-label dose escalation; BRAF inhibitor; LEE011; CDK4/6; LGX818; RAF kinase inhibitor; Metastatic melanoma; BRAF; V600

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Approximately 23 months after enrollment

Secondary Outcomes (12)

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

  Approximately 23 months after enrollment

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

  Approximately 23 months after enrollment

• Phase Ib/II - Plasma Concentration-time Profiles

  28-day cycles

• Phase Ib/II - Overall Response Rate (ORR)

  Approximately 23 months after enrollment

• Phase Ib/II - Progression Free Survival (PFS)

  Approximately 23 months after enrollment

Study Arms (4)

Phase Ib

EXPERIMENTAL

Phase Ib will randomize 18 patients with BRAF mutant melanoma, who are naïve or who have progressed on prior therapy to evaluate the safety and tolerability of the combination of LEE011 and LGX818.

Drug: LEE011; Drug: LGX818

Phase II arm 1a

EXPERIMENTAL

Phase II arm 1a will randomize 60 patients that are naïve to prior BRAF inhibitor therapy to LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

Drug: LEE011; Drug: LGX818

Phase II arm 1b

EXPERIMENTAL

Phase II arm 1b will randomize 30 patients to LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

Drug: LGX818

Phase II arm 2

EXPERIMENTAL

Phase II arm 2 will evaluate a single arm LEE011+LGX818 in 40 patients resistant to prior BRAF inhibitor therapy. Single agent LGX818 has shown limited activity in patients with melanoma who have failed prior BRAF inhibitor treatment; the contribution of LEE011 in this combination will be evaluated.

Drug: LEE011; Drug: LGX818

Interventions

LEE011 DRUG

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

Also known as: Ribociclib

Phase II arm 1a; Phase II arm 2; Phase Ib

LGX818 DRUG

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

Also known as: Encorafenib

Phase II arm 1a; Phase II arm 1b; Phase II arm 2; Phase Ib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Array BioPharma: lead

Study Sites (9)

University of Colorado Dept of Oncology

Aurora, Colorado, 80045, United States

Location

Karmanos Cancer Institute Dept of Oncology

Detroit, Michigan, 48201, United States

Location

Memorial Sloan Kettering Cancer Center Dept Oncology

New York, New York, 90033, United States

Location

Oregon Health & Science University Dept. of OHSU (3)

Portland, Oregon, 97239, United States

Location

Vanderbilt University Medical Center SC - Dept of Oncology .

Nashville, Tennessee, 37232, United States

Location

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Woodville, South Australia, 5011, Australia

Location

Novartis Investigative Site

Montreal, Quebec, H2X 3J4, Canada

Location

Novartis Investigative Site

Utrecht, Netherlands, 3584CX, Netherlands

Location

MeSH Terms

Conditions

Melanoma

Interventions

ribociclib; encorafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

Study recruitment was halted on 07-Aug-2014 during the Phase Ib part of the study. The Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.

Results Point of Contact

• Title: Study Director
• Organization: Array BioPharma, Inc.

info@arraybiopharma.com

303-381-6604

Study Officials

• Array BioPharma

  303-381-6604

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2013
• First Posted: January 29, 2013
• Study Start: July 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: September 13, 2016
• Results First Posted: September 13, 2016

Record last verified: 2016-07

Locations

US (5); AU (2); CA (1); NL (1)