Trial Title:
A Study Comparing 3 Study Medicines (Encorafenib, Binimetinib, Pembrolizumab) to 2 Study Medicines (Ipilimumab and Nivolumab) in Patients With Advanced Melanoma
NCT ID:
NCT05926960
Condition:
Melanoma
Conditions: Official terms:
Melanoma
Pembrolizumab
Nivolumab
Ipilimumab
Conditions: Keywords:
BRAF
BRAF V600E/K melanoma
metastatic melanoma
advanced melanoma
skin cancer
portside
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
encorafenib
Description:
encorafenib
Arm group label:
Triplet
Other name:
BRAFTOVI
Intervention type:
Drug
Intervention name:
binimetinib
Description:
binimetinib
Arm group label:
Triplet
Other name:
MEKTOVI
Intervention type:
Drug
Intervention name:
pembrolizumab
Description:
pembrolizumab
Arm group label:
Triplet
Other name:
KEYTRUDA®
Intervention type:
Drug
Intervention name:
ipilimumab
Description:
ipilimumab
Arm group label:
Doublet
Other name:
YERVOY
Intervention type:
Drug
Intervention name:
nivolumab
Description:
nivolumab
Arm group label:
Doublet
Other name:
OPDIVO
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.
Detailed 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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fakultni nemocnice Hradec Kralove
Address:
City:
Hradec Kralove
Zip:
500 05
Country:
Czechia
Facility:
Name:
Fakultni nemocnice Ostrava
Address:
City:
Ostrava
Zip:
708 52
Country:
Czechia
Facility:
Name:
Fakultni nemocnice Olomouc
Address:
City:
Olomouc
Zip:
779 00
Country:
Czechia
Facility:
Name:
Fakultni nemocnice Bulovka
Address:
City:
Prague
Zip:
180 81
Country:
Czechia
Facility:
Name:
Vseobecna fakultni nemocnice v Praze
Address:
City:
Praha 2
Zip:
12808
Country:
Czechia
Facility:
Name:
Universitaetsklinikum Heidelberg
Address:
City:
Heidelberg
Zip:
69120
Country:
Germany
Facility:
Name:
Universitaetsklinikum Tuebingen
Address:
City:
Tübingen
Zip:
72076
Country:
Germany
Facility:
Name:
Universitätsklinikum Regensburg
Address:
City:
Regensburg
Zip:
93053
Country:
Germany
Facility:
Name:
Elbe Kliniken Stade-Buxtehude, Klinikum Buxtehude
Address:
City:
Buxtehude
Zip:
21614
Country:
Germany
Facility:
Name:
Medizinische Hochschule Hannover
Address:
City:
Hannover
Zip:
30625
Country:
Germany
Facility:
Name:
Universitaetsklinikum Essen
Address:
City:
Essen
Zip:
45147
Country:
Germany
Facility:
Name:
Fachklinik Hornheide
Address:
City:
Münster
Zip:
48157
Country:
Germany
Facility:
Name:
Universitätsmedizin Johannes Gutenberg Universität Mainz
Address:
City:
Mainz
Zip:
55131
Country:
Germany
Facility:
Name:
Universitätsklinikum Leipzig
Address:
City:
Leipzig
Zip:
04103
Country:
Germany
Facility:
Name:
Universitätsklinikum Schleswig-Holstein
Address:
City:
Lübeck
Zip:
23538
Country:
Germany
Facility:
Name:
HELIOS Klinikum Erfurt
Address:
City:
Erfurt
Zip:
99089
Country:
Germany
Facility:
Name:
SRH Wald-Klinikum Gera
Address:
City:
Gera
Zip:
07548
Country:
Germany
Facility:
Name:
Klinikum Bremen-Ost
Address:
City:
Bremen
Zip:
28325
Country:
Germany
Facility:
Name:
Istituto Nazionale Tumori Regina Elena
Address:
City:
Rome
Zip:
00144
Country:
Italy
Facility:
Name:
A.O.U. Policlinico Paolo Giaccone
Address:
City:
Palermo
Zip:
90127
Country:
Italy
Facility:
Name:
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
Address:
City:
Candiolo
Zip:
10060
Country:
Italy
Facility:
Name:
Azienda Ospedaliero Universitaria Senese
Address:
City:
Siena
Zip:
53100
Country:
Italy
Facility:
Name:
AO Santa Maria della Misericordia
Address:
City:
Perugia
Zip:
06132
Country:
Italy
Facility:
Name:
Istituto Oncologico Veneto IRCCS
Address:
City:
Padova
Zip:
35128
Country:
Italy
Facility:
Name:
Ospedale San Martino
Address:
City:
Genova
Zip:
16132
Country:
Italy
Facility:
Name:
Istituto Europeo di Oncologia IRCCS
Address:
City:
Milano
Zip:
20141
Country:
Italy
Facility:
Name:
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Facility:
Name:
Uniwersyteckie Centrum Kliniczne Klinika Chirurgii Onkologicznej, Transplantacyjnej i Ogólnej
Address:
City:
Gdansk
Zip:
80-214
Country:
Poland
Facility:
Name:
Pratia MCM Krakow
Address:
City:
Krakow
Zip:
30-727
Country:
Poland
Facility:
Name:
Samodzielny Publiczny Zakład Opieki Zdrowotnej MSWiA z Warmińsko - Mazurskim Centrum Onkologii
Address:
City:
Olsztyn
Zip:
10-228
Country:
Poland
Facility:
Name:
Uniwersytecki Szpital Kliniczny w Poznaniu
Address:
City:
Poznan
Zip:
60-780
Country:
Poland
Facility:
Name:
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Address:
City:
Warszawa
Zip:
02-781
Country:
Poland
Facility:
Name:
Fakultna Nemocnica s Poliklinikou F. D. Roosevelta Banska Bystrica
Address:
City:
Banska Bystrica
Zip:
975 17
Country:
Slovakia
Facility:
Name:
Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
Address:
City:
Banska Bystrica
Zip:
975 17
Country:
Slovakia
Facility:
Name:
Fakultna nemocnica s poliklinikou F.D. Roosevelta
Address:
City:
Banska Bystrica
Zip:
975 17
Country:
Slovakia
Facility:
Name:
Narodny onkologicky ustav
Address:
City:
Bratislava
Zip:
833 10
Country:
Slovakia
Facility:
Name:
Euromedix, a.s.
Address:
City:
Bratislava
Zip:
851 07
Country:
Slovakia
Facility:
Name:
Neovizia, s.r.o.
Address:
City:
Bratislava
Zip:
85101
Country:
Slovakia
Facility:
Name:
Institut nuklearnej a molekularnej mediciny
Address:
City:
Kosice
Zip:
042 53
Country:
Slovakia
Facility:
Name:
Martinske Biopticke centrum, s.r.o.
Address:
City:
Martin
Zip:
036 01
Country:
Slovakia
Facility:
Name:
DERMATOP s.r.o., MUDr. Frantisek Perutka
Address:
City:
Partizanske
Zip:
958 01
Country:
Slovakia
Facility:
Name:
Nemocnica na okraji mesta, n.o.
Address:
City:
Partizanske
Zip:
95801
Country:
Slovakia
Facility:
Name:
KARDIO, s.r.o.
Address:
City:
Poprad
Zip:
058 01
Country:
Slovakia
Facility:
Name:
MR Poprad s.r.o., Pracovisko magnetickej rezonancie
Address:
City:
Poprad
Zip:
058 01
Country:
Slovakia
Facility:
Name:
Nemocnica Poprad, a.s., Dermatovenerolgicka ambulancia
Address:
City:
Poprad
Zip:
058 01
Country:
Slovakia
Facility:
Name:
POKO Poprad, s.r.o., Ambulancia klinickej onkologie
Address:
City:
Poprad
Zip:
058 01
Country:
Slovakia
Facility:
Name:
Nemocnica Poprad, a.s.
Address:
City:
Poprad
Zip:
05801
Country:
Slovakia
Facility:
Name:
Ocne centrum Sokolik, s.r.o.
Address:
City:
Trencin
Zip:
91101
Country:
Slovakia
Facility:
Name:
H.R.U Málaga - Hospital General
Address:
City:
Malaga
Zip:
29010
Country:
Spain
Facility:
Name:
Hospital Germans Trias i Pujol
Address:
City:
Badalona
Zip:
08916
Country:
Spain
Facility:
Name:
Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Facility:
Name:
Institut Català d'Oncologia - L'Hospitalet
Address:
City:
L'Hospitalet de Llobregat
Zip:
08908
Country:
Spain
Facility:
Name:
Hospital General Universitario de Valencia
Address:
City:
Valencia
Zip:
46014
Country:
Spain
Facility:
Name:
Hospital General Universitario de Alicante
Address:
City:
Alicante
Zip:
03010
Country:
Spain
Facility:
Name:
Hospital Clínic de Barcelona
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Facility:
Name:
Hospital General Universitario Gregorio Marañon
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen Macarena
Address:
City:
Sevilla
Zip:
41009
Country:
Spain
Facility:
Name:
Hospital Universitario Miguel Servet
Address:
City:
Zaragoza
Zip:
50009
Country:
Spain
Facility:
Name:
Addenbrooke's Hospital
Address:
City:
Cambridge
Zip:
CB2 0QQ
Country:
United Kingdom
Facility:
Name:
Royal Marsden Hospital (Chelsea)
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Facility:
Name:
Royal Marsden Hospital (Sutton)
Address:
City:
London
Zip:
SM2 5PT
Country:
United Kingdom
Facility:
Name:
City Hospital, Nottingham University Hospitals NHS Trust
Address:
City:
Nottingham
Zip:
NG5 1PB
Country:
United Kingdom
Start date:
June 13, 2023
Completion date:
May 23, 2027
Lead sponsor:
Agency:
Pfizer
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Pfizer
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05926960
https://pmiform.com/clinical-trial-info-request?StudyID=C4221023
