A Study Comparing 3 Study Medicines (Encorafenib, Binimetinib, Pembrolizumab) to 2 Study Medicines (Ipilimumab and Nivolumab) in Patients With Advanced Melanoma

NCT05926960 | Terminated Phase 2 FDA Drug

• 4 other identifiers: C4221023KEYNOTE PNC92; PORTSIDE2023-509471-17-00MK-3475-C92
• Study Type: interventional
• Target: 38
• Locations: 5 countries
• Sites: 24

Brief Summary

The purpose of this study is to learn about the effects of 3 study medicines (encorafenib, binimetinib, pembrolizumab) compared to 2 study medicines (ipilimumab and nivolumab) given for the treatment of melanoma. Melanoma is a type of cancer that starts in the cells that give color to your skin. The study is seeking participants who:

• have advanced or metastatic melanoma (has spread to other parts of the body);
• have a certain abnormal gene called "BRAF".
• have taken nivolumab or pembrolizumab treatment before this study. Participants will either receive:
• pembrolizumab given by intravenous infusion (directly into a vein) every 3 weeks at the study clinic. Participants will also receive encorafenib and binimetinib by mouth every day at home,
• or will receive ipilimumab and nivolumab given by intravenous infusion (directly into a vein) every 3 weeks at the study clinic 4 times. This will be followed by nivolumab given by intravenous infusion every 4 weeks at the study clinic. Both pembrolizumab and nivolumab will be given for a maximum of around 2 years. However, there is no time limit for encorafenib and binimetinib treatment. The study team will see how each participant is doing after receiving the study treatments during regular visits to the study clinic.

Conditions

Melanoma

Keywords

BRAF; BRAF V600E/K melanoma; metastatic melanoma; advanced melanoma; skin cancer; portside

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) is defined as the proportion of participants in each treatment arm with a confirmed best overall response of either Complete Response (CR) or Partial Response (PR), as determined by investigator assessment per RECIST v1.1

  Time from the date of randomization to the earliest date disease progression, or start of subsequent anticancer therapy, or death due to any cause (assessed up to approximately 48 months).

Secondary Outcomes (10)

• Progression Free Survival in each treatment arm

  Time from the date of randomization to the earliest date of disease progression, as determined by investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first (assessed up to approximately 48 months)

• Overall Survival in each treatment arm

  Time from date of randomization to the date of death due to any cause or the last known alive date (assessed up to approximately 48 months)

• Duration of Response (CR or PR) in each treatment arm

  Time from the date of the first documented response (CR or PR) to the earliest date of disease progression, as determined by investigator assessment per RECIST v1.1, or death due to any cause (assessed up to approximately 48 months)

• Disease Control Rate (proportion of participants with a confirmed best overall response of CR, PR or SD) in each treatment arm

  Time from the date of randomization to the earliest date of disease progression, or start of subsequent anticancer therapy (assessed up to approximately 48 months)

• Time to Response (CR or PR)

  Time from the date of randomization to the date of first documented response (CR or PR), as determined by investigator assessment per RECIST v1.1 (assessed up to approximately 48 months)

Study Arms (2)

Triplet

EXPERIMENTAL

encorafenib and binimetinib in combination with pembrolizumab

Drug: encorafenib; Drug: binimetinib; Drug: pembrolizumab

Doublet

ACTIVE COMPARATOR

ipilimumab and nivolumab

Drug: ipilimumab; Drug: nivolumab

Interventions

encorafenib DRUG

encorafenib

Also known as: BRAFTOVI

Triplet

binimetinib DRUG

binimetinib

Also known as: MEKTOVI

Triplet

pembrolizumab DRUG

pembrolizumab

Also known as: KEYTRUDA®

Triplet

ipilimumab DRUG

ipilimumab

Also known as: YERVOY

Doublet

nivolumab DRUG

nivolumab

Also known as: OPDIVO

Doublet

Eligibility Criteria

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

You may qualify if:

• Male or female participants ≥18 years of age at the time of informed consent.
• Histologically confirmed unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, according to the AJCC 8th edition.
• Documented evidence of a BRAF V600E or V600K mutation.
• Availability of adequate tumor tissue (archival or newly obtained; block or slides) to submit to the sponsor central laboratory(ies) during the screening period for central biomarker analyses .
• Must have received only 1 prior line of systemic therapy for melanoma (either adjuvant therapy or first-line anti-PD-1 monotherapy (ie, nivolumab or pembrolizumab)
• Must have anti-PD-1 resistant disease (primary or secondary) with confirmed disease progression per RECIST v1.1 either during or after receipt of an approved anti-PD-1 monotherapy (ie, nivolumab or pembrolizumab) for melanoma, defined according to the SITC Immunotherapy Resistance Taskforce (Kluger et al, 2020).
• Have at least one measurable lesion per RECIST v1.1.
• ECOG PS of 0-1, and adequate organ and cardiac function, including LVEF ≥50% by cardiac imaging.

You may not qualify if:

• Mucosal or ocular melanoma.
• Diagnosis of immunodeficiency or an active autoimmune disease that required systemic treatment with chronic systemic steroid therapy or any other form of immunosuppressive therapy within the past 2 years.
• Clinically significant cardiovascular diseases.
• History of thromboembolic or cerebrovascular events ≤12 weeks prior to randomization.
• History or current evidence of RVO or current risk factors for RVO.
• Concurrent neuromuscular disorder that is associated with the potential of elevated CK.
• Active bacterial, fungal, or viral infection requiring systemic therapeutic treatment within 2 weeks prior to randomization.
• Current non-infectious pneumonitis/interstitial lung disease or history of noninfectious pneumonitis/interstitial lung disease requiring steroids.
• Prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases.
• Participants who permanently discontinued prior anti-PD-1 therapy due to toxicity or will be unable to tolerate combination therapy based on investigator judgement are excluded.
• Prior treatment with ipilimumab; prior combined immunotherapy blockade with anti-PD-1/L-1; prior treatment with a BRAFi and/or MEKi; or previous administration of an investigational anti-cancer agent for the adjuvant or first-line treatment of melanoma prior to randomization.

Sponsors & Collaborators

• Pfizer: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (24)

Universitaetsklinikum Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Fachklinik Hornheide

Münster, North Rhine-Westphalia, 48157, Germany

Location

Universitätsmedizin Johannes Gutenberg Universität Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Istituto Nazionale Tumori Regina Elena

Rome, ROMA, 00144, Italy

Location

A.O.U. Policlinico Paolo Giaccone

Palermo, Sicily, 90127, Italy

Location

Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia

Candiolo, Torino, 10060, Italy

Location

Azienda Ospedaliero Universitaria Senese

Siena, Tuscany, 53100, Italy

Location

AO Santa Maria della Misericordia

Perugia, Umbria, 06132, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, Veneto, 35128, Italy

Location

Istituto Europeo di Oncologia IRCCS

Milan, 20141, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Naples, 80131, Italy

Location

Pratia MCM Krakow

Krakow, 30-727, Poland

Location

Narodny onkologicky ustav

Bratislava, 833 10, Slovakia

Location

Neovizia, s.r.o.

Bratislava, 85101, Slovakia

Location

Hospital Germans Trias i Pujol

Badalona, Barcelona [barcelona], 08916, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [barcelona], 08035, Spain

Location

Institut Català d'Oncologia - L'Hospitalet

L'Hospitalet de Llobregat, Catalunya [cataluña], 08908, Spain

Location

Hospital General Universitario de Valencia

Valencia, Valenciana, Comunitat, 46014, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

encorafenib; binimetinib; pembrolizumab; Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2023
• First Posted: July 3, 2023
• Study Start: June 13, 2023
• Primary Completion: February 2, 2026
• Study Completion: February 2, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

PL (1); SL (2); ES (7); DE (6); IT (8)