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A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma

Primary Purpose

Melanoma

Status

Recruiting

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Encorafenib

Binimetinib

Pembrolizumab

About this trial

This is an interventional treatment trial for Melanoma focused on measuring BRAF V600E/K Melanoma, BRAF, Melanoma, Advanced Melanoma, Metastatic Melanoma, Skin Cancer, Advanced Skin Cancer, Starboard, Stage 3 Melanoma, Stage 4 Melanoma, BRAF Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female participants ≥ 18 years at the time of informed consent.
Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
Histologically confirmed unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, according to the AJCC 8th edition.
Presence of at least 1 measurable lesion as detected by radiological and/or photographic methods according to RECIST v1.1.
ECOG performance status 0 or 1.
Documented evidence of a BRAF V600E or V600K mutation in melanoma tumor tissue as previously determined by either PCR or NGS-based local laboratory assay (eg, US FDA-approved test, CE-marked [European conformity] in vitro diagnostic in EU countries, or equivalent), obtained during the course of normal clinical care, in a CLIA- or similarly certified laboratory.
Submission of adequate tumor tissue (archival or newly obtained; block or slides to the sponsor central laboratory(ies) during the screening period and prior to enrollment (SLI)/randomization (Phase 3).
Have not received prior first-line systemic therapy for metastatic or unresectable locally advanced melanoma.
Adequate bone marrow function, hepatic and renal function.
Capable of giving signed informed consent.

Exclusion Criteria

Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
Mucosal or ocular melanoma.
Diagnosis of immunodeficiency or an active autoimmune disease that required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear IgA dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
Unable to swallow, retain, and absorb oral medications.
Impairment of GI function or disease which may significantly alter the absorption of oral study intervention (eg, uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, including malabsorption syndrome secondary to prior GI surgery).
Clinically significant cardiovascular diseases,
History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to enrollment (SLI)/randomization (Phase 3). Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (ie, massive or sub-massive) deep vein thrombosis or pulmonary emboli.
History or current evidence of RVO or current risk factors for RVO (eg, uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
Concurrent neuromuscular disorder that is associated with the potential of elevated CK (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
Current noninfectious pneumonitis or history of noninfectious pneumonitis requiring steroids, or history of radiation pnuemonitis
Evidence of HBV or HCV infection.
Known history of a positive test for HIV or known AIDS.
Any active infection requiring systemic therapeutic treatment within 2 weeks prior to enrollment (SLI)/ randomization (Phase 3).
Participants with prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases.
Concurrent or previous other malignancy within 2 years of study entry, except curatively treated basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, Bowen's disease and Gleason ≤ 6 prostate cancer. Participants with a history of other curatively treated cancers must be reviewed with the sponsor or designee prior to entering the study.
Participants who previously received and subsequently discontinued encorafenib and/or binimetinib and/or anti-PD-1/-L1 due to severe toxicity.
For participants in the SLI only: Current use or anticipated need for food or drugs that are known moderate or strong CYP3A4 inhibitors during screening and through the DLT-evaluation period
Participant has not recovered to Grade ≤ 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before enrollment (SLI)/ randomization (Phase 3).
Receipt of protocol defined medications or treatments outside of required intervals before enrollment (SLI)/randomization (Phase 3):
Previous administration with an investigational drug ≤ 6 months prior to enrollment (SLI)/randomization (Phase 3).
Known sensitivity or contraindication to any component of study intervention (encorafenib, binimetinib and pembrolizumab), or their excipients.
Pregnant, confirmed by a positive β-hCG laboratory test result, or is breastfeeding (lactating).
Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Sites / Locations

UCLA - Hematology/Oncology - Administrative OfficeRecruiting
Ronald Reagan UCLA Medical Center Drug Information Center , Dept. of Pharmaceutical Services (DrugRecruiting
Ronald Reagan UCLA Medical Center, Drug Information Center, Dept. of Pharmaceutical Services (Main ORecruiting
UCLA Hematology/Oncology - Westwood (Building 100)Recruiting
UCHealth Sue Anschutz-Rodgers Eye CenterRecruiting
University of Colorado Denver CTO/CTRCRecruiting
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)Recruiting
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)Recruiting
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)Recruiting
Florida Cancer SpecialistsRecruiting
Florida Cancer SpecialistsRecruiting
AdventHealth Orlando Infusion CenterRecruiting
AdventHealth Orlando, Investigational Drug ServicesRecruiting
AdventHealth OrlandoRecruiting
Advocate Medical Group-Park Ridge, Luther Lane-OncologyRecruiting
The University of Kansas Cancer CenterRecruiting
Massachusetts General HospitalRecruiting
Ophthalmic Consultants of Boston Inc (OCB)Recruiting
Revive Research Institute, Inc.Recruiting
Michigan Health ProfessionalsRecruiting
St. Vincent HealthcareRecruiting
St. Vincent Frontier Cancer CenterRecruiting
University of Cincinnati Medical CenterRecruiting
University of Cincinnati Medical CenterRecruiting
University of Tennessee Medical CenterRecruiting
Sarah Cannon Research InstituteRecruiting
Tennessee Oncology, PLLCRecruiting
Texas Oncology - CarrolltonRecruiting
North Dallas Eye AssociatesRecruiting
Texas Oncology - Flower MoundRecruiting
Baylor Clinic
Baylor College of Medicine Medical Center
Baylor College of Medicine
CHI St. Luke's Health Baylor College of Medicine Medical Center
Harris Health System - Ben Taub Hospital
Harris Health System - Smith Clinic
Dan Brown O.D.Recruiting
Texas Oncology-ParisRecruiting
Baylor Scott & White Medical Center - TempleRecruiting
Utah Cancer SpecialistsRecruiting
Utah Cancer SpecialistsRecruiting
Utah Cancer SpecialistsRecruiting
Utah Cancer SpecialistsRecruiting
Utah Cancer SpecialistsRecruiting
Utah Cancer SpecialistsRecruiting
Utah Cancer SpecialistsRecruiting
Utah Cancer SpecialistsRecruiting
Utah Cancer SpecialistsRecruiting
Utah Cancer SpecialistsRecruiting
Instituto Alexander FlemingRecruiting
Clinica Viedma S. ARecruiting
Instituto de Oncologia de RosarioRecruiting
Universitätsklinikum St. PöltenRecruiting
Ordensklinikum Linz GmbH ElisabethinenRecruiting
Medizinische Universität WienRecruiting
Medizinische Universität GrazRecruiting
UZ BrusselRecruiting
UZ GentRecruiting
AZ Sint-Jan Brugge-Oostende AVRecruiting
Cliniques universitaires Saint-LucRecruiting
Centre Hospitalier de JolimontRecruiting
VITAZRecruiting
Instituto de Oncologia do Paraná - IOP Matriz Mateus LemeRecruiting
Instituto de Oncologia do Paraná - IOP OncovilleRecruiting
Hospital de Clinicas de Porto AlegreRecruiting
Instituto Nacional de Câncer José Alencar Gomes da Silva - INCARecruiting
Hospital de Clínicas de Passo FundoRecruiting
Fundação Pio XII - Hospital de Câncer de Barretos
Fundação Pio XII - Hospital de Câncer de BarretosRecruiting
Hospital Sírio-Libanês - Unidade Bela VistaRecruiting
Complex Oncology Center - Plovdiv EOODRecruiting
Complex Oncology Center-Ruse EOODRecruiting
Medical Center Nadezhda Clinical EOODRecruiting
Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda EADRecruiting
Umhato EadRecruiting
Kingston Health Sciences Centre-Kingston General Hospital SiteRecruiting
CIUSSS du Saguenay-Lac-Saint-JeanRecruiting
McGill University Health Centre - Glen SiteRecruiting
Saskatoon Cancer CenterRecruiting
Fakultni nemocnice Olomouc
Olomouc University HospitalRecruiting
Masarykuv Onkologicky UstavRecruiting
Fakultni nemocnice Hradec KraloveRecruiting
Fakultni nemocnice Ostrava
Fakultni nemocnice OstravaRecruiting
Všeobecná fakultní nemocniceRecruiting
Fakultni nemocnice BulovkaRecruiting
Tampereen yliopistollinen sairaalaRecruiting
Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)Recruiting
CHG Le MansRecruiting
Chu Charles NicolleRecruiting
CHU de Lille - Hôpital Claude Huriez ServiceRecruiting
CHU d'Amiens - Hôpital NordRecruiting
CHU d'AngersRecruiting
Hôpital Saint AndréRecruiting
Hôpital Ambroise ParéRecruiting
Hôpital Ambroise ParéRecruiting
CHU de Dijon BourgogneRecruiting
CHU Grenoble AlpesRecruiting
CHG Le MansRecruiting
CHU de Lille - Hôpital Claude Huriez ServiceRecruiting
Hôpital de la TimoneRecruiting
Hôpital Lyon SudRecruiting
CHU de PoitiersRecruiting
Hôpital Charles Nicolle - CHU de RouenRecruiting
CHU de Saint-Etienne - Hôpital NordRecruiting
Gustave RoussyRecruiting
Universitaetsklinikum TuebingenRecruiting
Universitaetsklinikum ErlangenRecruiting
Klinik und Poliklinik für Dermatologie und AllergologieRecruiting
Elbe Kliniken Stade-Buxtehude, Klinikum BuxtehudeRecruiting
Universitätsklinikum Bonn
Johannes Wesling Klinikum MindenRecruiting
Universitätsmedizin Johannes Gutenberg Universität MainzRecruiting
Universitaetsklinikum Carl Gustav Carus DresdenRecruiting
Universitätsklinikum LeipzigRecruiting
Universitaetsklinikum Schleswig-Holstein Campus KielRecruiting
Universitätsklinikum Schleswig-HolsteinRecruiting
SRH Wald-Klinikum GeraRecruiting
Charité Universitaetsmedizin Berlin - Campus MitteRecruiting
Vivantes Klinikum NeuköllnRecruiting
Helios Klinikum ErfurtRecruiting
Universitätsklinikum Essen (AöR)Recruiting
Universitaetsklinikum Halle - Universitaetsklinik und Poliklinik fuer Dermatologie und VenerologieRecruiting
Universitaetsklinikum Hamburg-EppendorfRecruiting
Medizinische Hochschule HannoverRecruiting
Universitätsklinikum HeidelbergRecruiting
University Hospital MuensterRecruiting
Fachklinik HornheideRecruiting
Klinikum Nürnberg NordRecruiting
Universitätsklinikum RegensburgRecruiting
General Hospital of Athens "Laiko"Recruiting
Laiko HospitalRecruiting
Metropolitan HospitalRecruiting
University General Hospital of HeraklionRecruiting
Bioclinic Thessalonikis Private Clinic Single Member S.A.Recruiting
Pécsi Tudományegyetem Klinikai KözpontRecruiting
Semmelweis EgyetemRecruiting
Orszagos Onkologiai IntezetRecruiting
Debreceni Egyetem Klinikai KozpontRecruiting
Szent-Gyorgyi Albert Klinikai KozpontRecruiting
Jász-Nagykun-Szolnok Megyei Hetényi Géza KórházRecruiting
Ha'emek Medical Center.Recruiting
Soroka University Medical CenterRecruiting
Hadassah Medical Organization, Hadassah Medical Center, Ein-KaremRecruiting
Rabin Medical Center, Beilinson HospitalRecruiting
The Chaim Sheba Medical CenterRecruiting
Tel Aviv Sourasky Medical CenterRecruiting
Azienda Sanitaria Universitaria Friuli CentraleRecruiting
Fondazione IRCCS Istituto Nazionale dei TumoriRecruiting
Istituto Dermopatico dell'Immacolata (IDI-IRCCS)Recruiting
A.O.U.S. Policlinico "Le Scotte"Recruiting
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'OncologiaRecruiting
Istituto Tumori Giovanni Paolo IIRecruiting
IRCCS Ospedale Policlinico San MartinoRecruiting
Istituto Europeo di Oncologia IRCCSRecruiting
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"Recruiting
Istituto Oncologico Veneto IOV - IRCCSRecruiting
AO di Perugia - Ospedale S. Maria della Misericordia, S.C Oncologia MedicaRecruiting
Istituto Nazionale Tumori Regina ElenaRecruiting
ONCARE Viaducto NápolesRecruiting
Preparaciones Oncológicas S.C.Recruiting
I Can Oncology Center S.A. de C.V.Recruiting
BRCR Global Mexico - CDMXRecruiting
El Cielo Medical Center RSB, S.CRecruiting
El Cielo Medical CenterRecruiting
New Zealand Clinical Research (Christchurch)Recruiting
Palmerston North HospitalRecruiting
Auckland City HospitalRecruiting
Akershus UniversitetssykehusRecruiting
Oslo universitetssykehus, RadiumhospitaletRecruiting
Jagiellońskie Centrum Innowacji Sp. z o .o.Recruiting
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o .o.Recruiting
Szpital Kliniczny im. Heliodora Święcickiego UM w PoznaniuRecruiting
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut BadawczyRecruiting
Private Medical Institution "Euromedservice"
Ars Medika Center, LLC
BIH of Omsk Region "Clinical Oncological Dispensary"
Eurocityclinic LLC
Fakultná nemocnica s poliklinikou F.D. Roosevelta Banská BystricaRecruiting
Onkologicky ustav sv. Alzbety, s.r.o.Recruiting
Narodny onkologicky ustavRecruiting
Vychodoslovensky onkologicky ustav, a.s.Recruiting
Nemocnica na okraji mesta, n.o.Recruiting
POKO Poprad, s.r.o.Recruiting
Wits Clinical ResearchRecruiting
Sandton Oncology Medical Group (Pty) LtdRecruiting
Drs Alberts, Bouwer and Jordaan Inc.Recruiting
Mary Potter Oncology CentreRecruiting
CHUS - Hospital Clinico UniversitarioRecruiting
ICO-Badalona Hospital Germans Trias i PujolRecruiting
Hospital Universitario Marqués de ValdecillaRecruiting
Hospital Universitario Puerta de Hierro MajadahondaRecruiting
Hospital Clinico Universitario Virgen de la ArrixacaRecruiting
Complejo Hospitalario De NavarraRecruiting
CHUAC-Hospital Teresa HerreraRecruiting
Hospital Universitari Vall D'Hebron, Servicio de Oncología MédicaRecruiting
Hospital Clinic Barcelona
Hospital de la Santa Creu i Sant PauRecruiting
Hospital Universitario Reina Sofía
Complejo Hospitalario de JaenRecruiting
Hospital Universitario Arnau de VilanovaRecruiting
Hospital General Universitario Gregorio MarañónRecruiting
Hospital Universitario Ramón y CajalRecruiting
Hospital Regional Universitario de Malaga - Hospital CivilRecruiting
Hospital Universitario Virgen MacarenaRecruiting
Hospital Universitario Virgen del RocioRecruiting
Fundacion Instituto Valenciano de OncologiaRecruiting
Hospital Universitario Miguel ServetRecruiting
Kantonsspital WinterthurRecruiting
UniversitätsSpital ZürichRecruiting
Istanbul University Cerrahpasa Medical Faculty HospitalRecruiting
Medipol Mega Universite HastanesiRecruiting
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir HastanesiRecruiting
Memorial Ankara HastanesiRecruiting
Ankara Şehir HastanesiRecruiting
Medical and diagnostic center of MedX-Ray International Group Limited Liability Company Israeli
Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council
Municipal non-profit enterprise Khmelnytsky regional antitumor center of Khmelnytsky regional
Municipal non-profit enterprise "Kyiv City Clinical Hospital No. 2" of the executive body of the
National Cancer Institute
Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Oncological Regional Therapeutica
Derzhavna ustanova Instytut zahalnoi ta nevidkladnoi khirurhii im.V.T.Zaitseva Natsionalnoi akademii
Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasnyi klinichnyi spetsializovan
Municipal non-profit enterprise "Zaporizhzhia Regional Antitumor Center" Zaporizhzhya Regional Counc
Nottingham University Hospitals NHS TrustRecruiting
St. Bartholomew's Hospital, Barts Health NHS TrustRecruiting
Nottingham University Hospitals NHS TrustRecruiting
The South West Wales Cancer Institute, Swansea Bay University Health BoardRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Triplet Arm

Control Arm

Arm Description

Encorafenib and Binimetinib in combination with Pembrolizumab

Pembrolizumab

Outcomes

Primary Outcome Measures

Safety Lead In (SLI): Incidence of Dose Limiting Toxicities (DLTs)

A DLT is defined as any adverse event or laboratory value that is assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring within the first 2 cycles of treatment.

Phase 3: Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)

PFS is defined as the time from the date of randomization to the first date of documented disease progression as determined by BICR assessment per RECIST 1.1 or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Safety Lead in (SLI) and Phase 3: Incidence and severity of Adverse Events (AEs) and changes in clinical laboratory parameters, vital signs, and cardiac assessments.

AEs, laboratory parameters, vital signs and cardiac abnormalities will be graded according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 4.03).

Safety Lead in (SLI) and Phase 3: Objective Response Rate (ORR)

ORR is defined as the proportion of participants with a confirmed BOR of either CR or PR, as determined by BICR and investigator assessment per RECIST v1.1

Safety Lead in (SLI) and Phase 3: Disease Control Rate (DCR)

DCR is defined as the proportion of participants with a confirmed BOR of CR, PR or SD, as determined by BICR and investigator assessment per RECIST v1.1.

Safety Lead in (SLI) and Phase 3: Time to Response (TTR)

TTR is defined as the time from the date of randomization to the date of first documented response (CR or PR), as determined by BICR and investigator or assessment per RECIST v1.1.

Phase 3: Overall Survival (OS)

OS is defined as the time from the date of randomization to the date of death due to any cause

Phase 3: Progression Free Survival (PFS) by Investigator

PFS by investigator is defined as the time from the date of randomization to the first date of documented disease progression as determined by investigator assessment per RECIST 1.1 or death due to any cause, whichever occurs first.

Phase 3: Duration of Response (DOR)

DOR is defined as the time from the date of first documented response to the date of first documented disease progression, as determined by BICR and investigator assessment or death due to any cause, whichever occurs first.

Phase 3: Progression Free Survival 2 (PFS2)

PFS2 is defined as the time from the date of randomization to the date of discontinuation of next-line treatment after first objective disease progression by investigator assessment per RECIST v1.1

Safety Lead in (SLI): Plasma concentration-time profiles and Pharmacokinetic (PK) parameter estimates for encorafenib and binimetinib.

To measure plasma concentrations of encorafenib and its metabolite (LHY746), and binimetinib and its metabolite (AR00426032)

Phase 3: Plasma concentrations of encorafenib and binimetinib.

To measure the plasma concentrations of encorafenib and its metabolite (LHY746), and binimetinib and its metabolite (AR00426032)

Phase 3: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30): change from baseline in the global health status/QoL score.

EORTC QLQ-30 includes 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/Quality of Life scale

Phase 3: Change from baseline in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale score.

The FACT-M is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, melanoma-specific items, and items related to melanoma surgery

Phase 3: Change from baseline in 5-level EuroQol-5D (EQ-5D-5L) index score and visual analog scale (VAS)

The EQ-5D-5L is a standardized measure of health utility that provides a single index value of health status and contains 1 item for each of 5 dimensions of HRQoL (ie, mobility, self-care, usual activities, pain or discomfort, and anxiety or depression).

Phase 3: Change from baseline in Patient Global Impression of Severity (PGIS) score

The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe".

Phase 3: Patient Global Impression of Change (PGIC) score

The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change"

Full Information

NCT ID

NCT04657991

First Posted

December 1, 2020

Last Updated

September 8, 2023

Sponsor

Pfizer

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT04657991

Brief Title

A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma

Official Title

A PHASE 3, RANDOMIZED, DOUBLE-BLIND STUDY OF ENCORAFENIB AND BINIMETINIB PLUS PEMBROLIZUMAB VERSUS PLACEBO PLUS PEMBROLIZUMAB IN PARTICIPANTS WITH BRAF V600E/K MUTATION-POSITIVE METASTATIC OR UNRESECTABLE LOCALLY ADVANCED MELANOMA

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 15, 2021 (Actual)

Primary Completion Date

September 30, 2024 (Anticipated)

Study Completion Date

February 9, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to learn about the effects of three study medicines (encorafenib, binimetinib, and pembrolizumab) given together for the treatment of melanoma that: is advanced or metastatic (spread to other parts of the body); has a certain type of abnormal gene called "BRAF"; and has not received prior treatment. All participants in this study will receive pembrolizumab at the study clinic once every 3 weeks as an intravenous (IV) infusion (given directly into a vein). In addition, half of the participants will take encorafenib and binimetinib orally (by mouth) at home every day. Participants may receive pembrolizumab for up to two years. Those participants taking encorafenib and binimetinib can continue until their melanoma is no longer responding. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.

Detailed Description

This study will compare the efficacy, safety, and tolerability of encorafenib and binimetinib plus pembrolizumab (Triplet Arm) versus placebo plus pembrolizumab (Control Arm) in participants with metastatic or unresectable locally advanced BRAF V600E/K mutation-positive melanoma. The study will have an open-label safety lead-in (SLI) phase to determine the safety recommend Phase 3 dose (RP3D) and pharmacokinetics (PK) of encorafenib and binimetinib plus pembrolizumab combination therapy prior to initiation of the randomized Phase 3 part of the study. Two dose levels of encorafenib in combination with binimetinib plus pembrolizumab will be explored in parallel. A minimum of 12 evaluable participants will be enrolled per dose level. During the double-blind randomized Phase 3 part of the study, approximately 600 eligible participants will be randomized in a 1:1 ratio to the Triplet Arm (at RP3D determined in the SLI) or Control Arm (approximately 300 participants per arm). Randomization will be stratified by prior systemic adjuvant therapy and stage of disease by AJCC (ED8).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

BRAF V600E/K Melanoma, BRAF, Melanoma, Advanced Melanoma, Metastatic Melanoma, Skin Cancer, Advanced Skin Cancer, Starboard, Stage 3 Melanoma, Stage 4 Melanoma, BRAF Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

624 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Triplet Arm

Arm Type

Experimental

Arm Description

Encorafenib and Binimetinib in combination with Pembrolizumab

Arm Title

Control Arm

Arm Type

Active Comparator

Arm Description

Pembrolizumab

Intervention Type

Drug

Intervention Name(s)

Encorafenib

Other Intervention Name(s)

BRAFTOVI

Intervention Description

Encorafenib

Intervention Type

Drug

Intervention Name(s)

Binimetinib

Other Intervention Name(s)

MEKTOVI

Intervention Description

Binimetinib

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Other Intervention Name(s)

KEYTRUDA

Intervention Description

Pembrolizumab

Primary Outcome Measure Information:

Title

Safety Lead In (SLI): Incidence of Dose Limiting Toxicities (DLTs)

Description

Time Frame

First 2 Cycles of Treatment (cycles are 21 days)

Title

Phase 3: Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)

Description

Time Frame

Time from the date of randomization to the date of first documented disease progression, as determined by BICR assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks for 24 months)

Secondary Outcome Measure Information:

Title

Safety Lead in (SLI) and Phase 3: Incidence and severity of Adverse Events (AEs) and changes in clinical laboratory parameters, vital signs, and cardiac assessments.

Description

Time Frame

Time from first dose of study intervention through 28 days after the last dose of study intervention.

Title

Safety Lead in (SLI) and Phase 3: Objective Response Rate (ORR)

Description

ORR is defined as the proportion of participants with a confirmed BOR of either CR or PR, as determined by BICR and investigator assessment per RECIST v1.1

Time Frame

Time from the date after the first dose of first dose (SLI) or the date of randomization (Phase 3) until documented PD, or start of subsequent anticancer therapy (approximately every 9 weeks).

Title

Safety Lead in (SLI) and Phase 3: Disease Control Rate (DCR)

Description

DCR is defined as the proportion of participants with a confirmed BOR of CR, PR or SD, as determined by BICR and investigator assessment per RECIST v1.1.

Time Frame

Time from the date after the first dose of first dose (SLI) or the date of randomization (Phase 3) until documented PD, or start of subsequent anticancer therapy (approximately every 9 weeks)

Title

Safety Lead in (SLI) and Phase 3: Time to Response (TTR)

Description

TTR is defined as the time from the date of randomization to the date of first documented response (CR or PR), as determined by BICR and investigator or assessment per RECIST v1.1.

Time Frame

Time from the date of randomization to the date of first documented response (CR or PR), as determined by investigator assessment per RECIST v1 (approximately every 9 weeks)

Title

Phase 3: Overall Survival (OS)

Description

OS is defined as the time from the date of randomization to the date of death due to any cause

Time Frame

Time from the date of randomization to the date of death due to any cause.

Title

Phase 3: Progression Free Survival (PFS) by Investigator

Description

Time Frame

The time from the date of randomization to the date of first documented disease progression, as determined by investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks)

Title

Phase 3: Duration of Response (DOR)

Description

Time Frame

Time from date of first documented response (CR or PR) to the date of first documented disease progression, as determined by BICR and investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks)

Title

Phase 3: Progression Free Survival 2 (PFS2)

Description

PFS2 is defined as the time from the date of randomization to the date of discontinuation of next-line treatment after first objective disease progression by investigator assessment per RECIST v1.1

Time Frame

The time from the date of randomization to the date of discontinuation of next-line treatment after first objective disease progression by investigator assessment per RECIST v1.1 (approximately every 9 weeks)

Title

Safety Lead in (SLI): Plasma concentration-time profiles and Pharmacokinetic (PK) parameter estimates for encorafenib and binimetinib.

Description

To measure plasma concentrations of encorafenib and its metabolite (LHY746), and binimetinib and its metabolite (AR00426032)

Time Frame

Cycle 2, Day 1

Title

Phase 3: Plasma concentrations of encorafenib and binimetinib.

Description

To measure the plasma concentrations of encorafenib and its metabolite (LHY746), and binimetinib and its metabolite (AR00426032)

Time Frame

Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 (Each Cycle is 21 days)

Title

Phase 3: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30): change from baseline in the global health status/QoL score.

Description

Time Frame