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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05926960
Other study ID # C4221023
Secondary ID 2021-003640-24KE
Status Recruiting
Phase Phase 2
First received
Last updated
Start date June 13, 2023
Est. completion date May 23, 2027

Study information

Verified date May 2024
Source Pfizer
Contact Pfizer CT.gov Call Center
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

The purpose of the study is to compare the efficacy of a triplet therapy (encorafenib, binimetinib, pembrolizumab) versus a doublet/control therapy (nivolumab and ipilimumab). Participants will have metastatic or unresectable locally advanced BRAF V600E/K-mutant melanoma, which progressed during or after prior treatment in the adjuvant or first-line metastatic setting, with an approved anti-PD-1 monotherapy (pembrolizumab or nivolumab), Approximately 150 participants will be randomized in a 1:1 ratio to the triplet or the doublet/control therapy (75 participants in each arm). Randomization will be stratified by baseline serum LDH level, and by type of PD-1 resistance.


Recruitment information / eligibility

Status Recruiting
Enrollment 150
Est. completion date May 23, 2027
Est. primary completion date May 23, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - 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. Exclusion Criteria: - 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
encorafenib
encorafenib
binimetinib
binimetinib
pembrolizumab
pembrolizumab
ipilimumab
ipilimumab
nivolumab
nivolumab

Locations

Country Name City State
Czechia Fakultni nemocnice Hradec Kralove Hradec Kralove Hradec Králové
Czechia Fakultni nemocnice Olomouc Olomouc Olomoucký KRAJ
Czechia Fakultni nemocnice Ostrava Ostrava Moravskoslezský KRAJ
Czechia Fakultni nemocnice Bulovka Prague Praha 8
Czechia Vseobecna fakultni nemocnice v Praze Praha 2
Germany Klinikum Bremen-Ost Bremen
Germany Elbe Kliniken Stade-Buxtehude, Klinikum Buxtehude Buxtehude Niedersachsen
Germany Helios Klinikum Erfurt Erfurt Thüringen
Germany Universitaetsklinikum Essen Essen Nordrhein-westfalen
Germany SRH Wald-Klinikum Gera Gera Thüringen
Germany Medizinische Hochschule Hannover Hannover Niedersachsen
Germany Universitaetsklinikum Heidelberg Heidelberg Baden-württemberg
Germany Universitätsklinikum Leipzig Leipzig Sachsen
Germany Universitätsklinikum Schleswig-Holstein Lübeck Schleswig-holstein
Germany Universitätsmedizin Johannes Gutenberg Universität Mainz Mainz Rheinland-pfalz
Germany Fachklinik Hornheide Münster Nordrhein-westfalen
Germany Universitätsklinikum Regensburg Regensburg Bayern
Germany Universitaetsklinikum Tuebingen Tübingen Baden-württemberg
Italy Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia Candiolo Torino
Italy Ospedale San Martino Genova
Italy Istituto Europeo di Oncologia IRCCS Milano
Italy Istituto Nazionale Tumori IRCCS Fondazione Pascale Napoli
Italy Istituto Oncologico Veneto IRCCS Padova Veneto
Italy A.O.U. Policlinico Paolo Giaccone Palermo Sicilia
Italy AO Santa Maria della Misericordia Perugia Umbria
Italy Istituto Nazionale Tumori Regina Elena Rome Roma
Italy Azienda Ospedaliero Universitaria Senese Siena Toscana
Poland Uniwersyteckie Centrum Kliniczne Klinika Chirurgii Onkologicznej, Transplantacyjnej i Ogólnej Gdansk
Poland Pratia MCM Krakow Krakow
Poland Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z Warminsko - Mazurskim Centrum Onkologii Olsztyn
Poland Uniwersytecki Szpital Kliniczny w Poznaniu Poznan
Poland Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy Warszawa
Slovakia Fakultna Nemocnica s Poliklinikou F. D. Roosevelta Banska Bystrica Banska Bystrica
Slovakia Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
Slovakia Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica Banska Bystrica
Slovakia Euromedix, a.s. Bratislava
Slovakia Narodny onkologicky ustav Bratislava
Slovakia Neovizia, s.r.o. Bratislava
Slovakia Institut nuklearnej a molekularnej mediciny Kosice
Slovakia Martinske Biopticke centrum, s.r.o. Martin
Slovakia DERMATOP s.r.o., MUDr. Frantisek Perutka Partizanske
Slovakia Nemocnica na okraji mesta, n.o. Partizanske
Slovakia KARDIO, s.r.o. Poprad
Slovakia MR Poprad s.r.o., Pracovisko magnetickej rezonancie Poprad
Slovakia Nemocnica Poprad, a.s. Poprad
Slovakia Nemocnica Poprad, a.s., Dermatovenerolgicka ambulancia Poprad
Slovakia POKO Poprad, s.r.o., Ambulancia klinickej onkologie Poprad
Slovakia Ocne centrum Sokolik, s.r.o. Trencin
Spain Hospital General Universitario de Alicante Alicante
Spain Hospital Germans Trias i Pujol Badalona Barcelona [barcelona]
Spain Hospital Clínic de Barcelona Barcelona
Spain Hospital Universitari Vall d'Hebron Barcelona Barcelona [barcelona]
Spain Institut Català d'Oncologia - L'Hospitalet L'Hospitalet de Llobregat Catalunya [cataluña]
Spain Hospital General Universitario Gregorio Marañon Madrid
Spain Hospital Universitario 12 de Octubre Madrid
Spain H.R.U Málaga - Hospital General Malaga Andalucía
Spain Hospital Universitario Virgen Macarena Sevilla
Spain Hospital General Universitario de Valencia Valencia Valenciana, Comunitat
Spain Hospital Universitario Miguel Servet Zaragoza
United Kingdom Addenbrooke's Hospital Cambridge Cambridgeshire
United Kingdom Royal Marsden Hospital (Chelsea) London Kensington AND Chelsea
United Kingdom Royal Marsden Hospital (Sutton) London Sutton
United Kingdom City Hospital, Nottingham University Hospitals NHS Trust Nottingham

Sponsors (2)

Lead Sponsor Collaborator
Pfizer Merck Sharpe & Dohme LLC

Countries where clinical trial is conducted

Czechia,  Germany,  Italy,  Poland,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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)
Secondary 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)
Secondary 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)
Secondary 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)
Secondary 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)
Secondary Progression Free Survival 2 in each treatment arm Time from date of randomization to date of discontinuation of next-line treatment after 1st disease progression, 2nd disease progression after initiation of next line treatment, or death due to any cause (assessed up to approximately 48 months)
Secondary Incidence and severity of Adverse Events (AEs) and changes in clinical laboratory parameters, vital signs, and cardiac assessments. Number of participants with treatment emergent Adverse Events as as assessed per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 4.03). Time from first dose of study intervention through 28 days after the last dose of study intervention
Secondary Patient Reported Outcomes using EORTC QLQ-C30 questionnaires in each treatment arm EORTC (European Organization for Research and Treatment of Cancer) 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 Change from Baseline until Progressive Disease, death, withdrawal of consent, lost to follow-up, or end of study, whichever occurs first (assessed up to approximately 48 months)
Secondary Patient Reported Outcomes using EuroQOL EQ-5D-5L questionnaires in each treatment arm 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). Change from Baseline until Progressive Disease, death, withdrawal of consent, lost to follow-up, or end of study, whichever occurs first (assessed up to approximately 48 months)
Secondary BRAF V600E/K Variant Allele Frequency and/or overall mean Variant Allele Frequency from circulating tumour DNA analysis in each treatment arm Change from baseline, Day 1 of Cycle 2 (after 3 weeks), and End of Treatment (assessed up to approximately 48 months)
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