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

Melanoma Clinical Trial

— PORTSIDE  

Official title:

A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF ENCORAFENIB AND BINIMETINIB PLUS PEMBROLIZUMAB VERSUS NIVOLUMAB AND IPILIMUMAB IN PARTICIPANTS WITH BRAF V600E/K MUTATION-POSITIVE MELANOMA WHO PROGRESSED DURING OR AFTER PRIOR TREATMENT WITH ANTI-PD-1 THERAPY

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05926960
• Other study ID #: C4221023
• Secondary ID: 2021-003640-24KE
• Status: Recruiting
• Phase: Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• Melanoma

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)

External Links

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