Clinical trial • Phase I|Phase III • Oncology

ENCORAFENIB for Metastatic or unresectable locally advanced melanoma (BRAF V600E/K mutation-positive)

Phase I|Phase III trial of ENCORAFENIB for Metastatic or unresectable locally advanced melanoma (BRAF V600E/K mutation-positive).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Metastatic or unresectable locally advanced melanoma (BRAF V600E/K mutation-positive)
Trial Stage
Phase I|Phase III
Drug Modality
Small molecule|Monoclonal antibody

Key dates

Initial CTIS Submission Date
30-04-2024
First CTIS Authorization Date
29-05-2024

Trial design

Randomised, placebo plus pembrolizumab (keytruda 25 mg/ml concentrate for solution for infusion; pembrolizumab listed with max total amount 200 mg iv).-controlled, adaptive Phase I|Phase III trial in Poland, Hungary, Italy and others.

Randomised
Yes
Comparator
Placebo plus pembrolizumab (KEYTRUDA 25 mg/mL concentrate for solution for infusion; pembrolizumab listed with max total amount 200 mg IV).
Adaptive
True - Safety Lead-In dose-escalation to determine the RP3D of encorafenib and binimetinib when given in combination with pembrolizumab (SLI). No further adaptive rules or interim analysis/stopping rules provided in the CTIS summary.
Biomarker Stratified
True, biomarker: BRAF V600E/K mutation (participants must have documented BRAF V600E or V600K mutation; strata by V600E vs V600K evident in inclusion criterion).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
67
Trial Duration For Participant
730

Eligibility

Recruits 67 The trial enrols adults (participants ≥18 years). The CTIS metadata flags vulnerable population selection as true, and detailed subject information and informed consent forms are provided (country-specific ICDs/PIS documents listed in the trial documents). Consent must be provided by the participant (no assent procedures for minors described because minors are excluded)..

Vulnerable Population
The trial enrols adults (participants ≥18 years). The CTIS metadata flags vulnerable population selection as true, and detailed subject information and informed consent forms are provided (country-specific ICDs/PIS documents listed in the trial documents). Consent must be provided by the participant (no assent procedures for minors described because minors are excluded).

Inclusion criteria

  • {"criterion_text":"- 1. Male or female participants ≥18 years of age at the time of informed consent."}
  • {"criterion_text":"- 2. Histologically confirmed unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, according to the AJCC 8th edition."}
  • {"criterion_text":"- 3. Documented evidence of a BRAF V600E or V600K mutation"}
  • {"criterion_text":"- 4. Submission of adequate tumor tissue for central laboratory testing of BRAF V600E/K mutation is required for all participants during the screening period and prior to enrollment (SLI)/randomization (Phase 3)."}
  • {"criterion_text":"- 5. SLI Participants: Have not received more than 1 prior systemic therapy for metastatic or locally advanced melanoma."}
  • {"criterion_text":"- 6. Phase 3 Participants: Have not received prior first-line systemic therapy for metastatic or unresectable locally advanced melanoma."}
  • {"criterion_text":"- 7. Have at least 1 measurable lesion per RECIST v1.1."}
  • {"criterion_text":"- 8. ECOG PS of 0 or 1, and adequate organ and cardiac function, including LVEF ≥50% by cardiac imaging."}

Exclusion criteria

  • {"criterion_text":"- 1. Mucosal or ocular melanoma"}
  • {"criterion_text":"- 10. Previous administration with an investigational drug ≤ 6 months prior to enrollment (SLI)/randomization (Phase 3)"}
  • {"criterion_text":"- 2. Diagnosis of immunodeficiency or an active autoimmune disease that required systemic treatment in the past 2 years."}
  • {"criterion_text":"- 3. Clinically significant cardiovascular disease."}
  • {"criterion_text":"- 4. History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to enrollment (SLI)/randomization (Phase 3)."}
  • {"criterion_text":"- 5. History or current evidence of RVO or current risk factors for RVO."}
  • {"criterion_text":"- 6. Concurrent neuromuscular disorder that is associated with the potential of elevated CK."}
  • {"criterion_text":"- 7. Any active infection requiring systemic therapeutic treatment within 2 weeks prior to enrollment (SLI)/ randomization (Phase 3)."}
  • {"criterion_text":"- 8. Current noninfectious pneumonitis/interstitial lung disease or history of noninfectious pneumonitis/interstitial lung disease requiring steroids, or history of radiation pneumonitis."}
  • {"criterion_text":"- 9. Prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Safety Lead-In: Incidence of DLTs.","definition_or_measurement_approach":"Incidence of dose-limiting toxicities (DLTs) during the Safety Lead-In period (no further definition provided in the CTIS summary)."}
  • {"endpoint_text":"- Randominzed Phase 3: OR, defined as confirmed BOR of either CR or PR, as determined by BICR assessment per RECIST v1.1 from randomization to the earliest of PD, start of subsequent anticancer therapy, or death due to any cause","definition_or_measurement_approach":"Overall response (OR) defined as confirmed best overall response (BOR) of complete response (CR) or partial response (PR) as determined by blinded independent central reviewer (BICR) using RECIST v1.1, measured from randomization to the earliest of documented progressive disease (PD), start of subsequent anticancer therapy, or death."}

Secondary endpoints

  • {"endpoint_text":"- 1. Safety Lead-In: Incidence and severity of AEs graded according to the NCI CTCAE v4.03* and changes in clinical laboratory parameters, vital signs, and cardiac assessments.","definition_or_measurement_approach":"Adverse events graded per NCI CTCAE v4.03; monitoring of clinical laboratory parameters, vital signs, and cardiac assessments."}
  • {"endpoint_text":"- 2. Safety Lead-In: OR, PFS, DC, TTR","definition_or_measurement_approach":"Objectives include overall response (OR), progression-free survival (PFS), disease control (DC), and time to response (TTR); specific definitions not detailed in the CTIS summary for this line."}
  • {"endpoint_text":"- 3. Safety Lead-In: Plasma concentration-time profiles and PK parameter estimates for encorafenib and binimetinib.","definition_or_measurement_approach":"Pharmacokinetic (PK) plasma concentration–time profiles and PK parameter estimates for encorafenib and binimetinib."}
  • {"endpoint_text":"- 4. Randomized Phase 3: PFS, defined as the 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.","definition_or_measurement_approach":"Progression-free survival (PFS) measured from randomization to first documented disease progression per BICR using RECIST v1.1, or death from any cause, whichever occurs first."}

Recruitment

Planned Sample Size
67
Recruitment Window Months
65
Consent Approach
Informed consent is required from participants (participants must be ≥18). Subject information and informed consent forms (ICDs/PIS) are provided as country- and language-specific documents (numerous ICD/PIS documents listed for participating countries). The participant provides consent; no assent process for minors is described.

Geography

Total Number Of Sites
54
Total Number Of Participants
161

Poland

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
31-05-2024
Processing Time Days
15
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Uniwersytecki Szpital Kliniczny W Poznaniu
Department Name
Oddział Kliniczny Onkologii Klinicznej i Doświadczalnej
Contact Person Name
Jacek Mackiewicz
Contact Person Email
jmackiewicz@ump.edu.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Nowotworów Tkanek Miękkich, Kości i Czerniaków
Contact Person Name
Piotr Rutkowski
Contact Person Email
piotr.rutkowski@pib-nio.pl

Hungary

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
04-06-2024
Processing Time Days
19
Number Of Sites
6
Number Of Participants
16

Sites

Site Name
University Of Debrecen
Department Name
Bőrgyógyászati Klinika
Contact Person Name
Gabriella Emri
Contact Person Email
gemri@med.unideb.hu
Site Name
University Of Szeged
Department Name
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ, Onkoterápiás Klinika
Contact Person Name
Judit Oláh
Contact Person Email
dr.olah.judit@gmail.com
Site Name
Semmelweis University
Department Name
Bor-, Nemikortani es Boronkologiai Klinika
Contact Person Name
Veronika Toth
Contact Person Email
toveroka@yahoo.com
Site Name
Orszagos Onkologiai Intezet
Department Name
Dermatoonkologiai Osztaly
Contact Person Name
Gabriella Liszkay
Contact Person Email
liszkay@oncol.hu
Site Name
Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet
Department Name
Onkologiai Kozpont
Contact Person Name
Hajnalka Nemeth
Contact Person Email
nemethhajnalka@hotmail.com
Site Name
University Of Pecs
Department Name
Nemikortani es Onkodermatologiai Klinika
Contact Person Name
Zsuzsanna Lengyel
Contact Person Email
lengyel.zsuzsanna@pte.hu

Italy

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
03-06-2024
Processing Time Days
18
Number Of Sites
11
Number Of Participants
38

Sites

Site Name
Azienda Ospedaliera Universitaria Senese
Department Name
U.O.C. Immunoterapia Oncologica
Contact Person Name
Michele Maio
Contact Person Email
mmaiocro@gmail.com
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
Oncologia Medica 1
Contact Person Name
Michelangelo Russillo
Contact Person Email
michelangelo.russillo@ifo.it
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Divisione di Oncologia Medica del Melanoma e Sarc
Contact Person Name
Filippo De Marinis
Contact Person Email
filippo.demarinis@ieo.it
Site Name
Istituto Tumori Bari Giovanni Paolo II
Department Name
Oncologia medica
Contact Person Name
Michele Guida
Contact Person Email
micguida57@gmail.com
Site Name
Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS
Department Name
Oncologia Medica
Contact Person Name
Fabrizio Carnevale Schianca
Contact Person Email
fabrizio.carnevale@ircc.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
UO Oncologia Medica 2
Contact Person Name
Francesco Spagnolo
Contact Person Email
francesco.spagnolo85@gmail.com
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
Oncologia Medica Melanoma Immunoterapia Oncologica e Terapie Innovative
Contact Person Name
Ester Simeone
Contact Person Email
ester.simeone@gmail.com
Site Name
Istituto Oncologico Veneto
Department Name
Medical Oncology 2
Contact Person Name
Luisa Piccin
Contact Person Email
luisa.piccin@iov.veneto.it
Site Name
Fondazione Luigi Maria Monti
Department Name
Unita Operativa Complessa
Contact Person Name
Federica De Galitiis
Contact Person Email
degalitiis@yahoo.it
Site Name
Hospital Santa Maria Della Misericordia
Department Name
Oncologia Medica
Contact Person Name
Mario Mandalà
Contact Person Email
mario.mandala@unipg.it
Site Name
Azienda Sanitaria Universitaria Friuli Centrale
Department Name
Oncology
Contact Person Name
Alessandro Minisini

Slovakia

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
29-05-2024
Processing Time Days
13
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Poko Poprad s.r.o.
Department Name
Ambulancia klinickej onkologie
Contact Person Name
Juraj Beniak
Contact Person Email
jurajbeniak1@gmail.com
Site Name
Vychodoslovensky Onkologicky Ustav a.s.
Department Name
Oddelenie klinickej onkologie
Contact Person Name
Maria Visnovska
Contact Person Email
visnovska@vou.sk
Site Name
National Oncology Institute
Department Name
Oddelenie klinickej onkologie E
Contact Person Name
Robert Godal
Contact Person Email
robert.godal@nou.sk

Spain

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
29-05-2024
Processing Time Days
13
Number Of Sites
9
Number Of Participants
26

Sites

Site Name
Hospital Universitario Regional De Malaga
Department Name
Servicio de Oncología
Contact Person Name
Elisabeth Perez Ruiz
Contact Person Email
eliperu@gmail.com
Site Name
Hospital Universitario Virgen De La Macarena
Department Name
Servicio de Oncologia Medica
Contact Person Name
Luis de la Cruz Merino
Contact Person Email
oncolcruz@gmail.com
Site Name
University Clinical Hospital Virgen De La Arrixaca
Department Name
Servicio de Oncologia
Contact Person Name
Pablo Cerezuela Fuentes
Contact Person Email
pcerezuelaf@seom.org
Site Name
Hospital Universitario Marques De Valdecilla
Department Name
Oncologia Medica
Contact Person Name
Marta Sotelo Garcia
Contact Person Email
m.sotelogarcia@gmail.com
Site Name
Hospital Germans Trias I Pujol
Department Name
Servicio de Oncologia
Contact Person Name
Sofia España Fernandez
Contact Person Email
sofia.ef@iconcologia.net
Site Name
Fundacion Instituto Valenciano De Oncologia
Department Name
Oncologia Medica
Contact Person Name
Maria Juan Fita
Contact Person Email
mjuanfi81@hotmail.com
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Servicio de Oncología Médica
Contact Person Name
Ricardo Cubedo Cervera
Contact Person Email
rcubedo@gmail.com
Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Servicio de Oncologia Medica
Contact Person Name
Maria Quindos Varela
Contact Person Email
Maria.Quindos.Varela@sergas.es
Site Name
Hospital Universitario Marques De Valdecilla (alternative listing)
Department Name
Oncologia Medica

Belgium

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
29-05-2024
Processing Time Days
13
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Cliniques Universitaires Saint-Luc
Contact Person Name
Jean-Francois Baurain

Finland

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
29-05-2024
Processing Time Days
13
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
HUS-Yhtymae
Department Name
Clinical Trial Unit
Contact Person Name
Micaela Hernberg
Contact Person Email
micaela.hernberg@hus.fi

Greece

Earliest CTIS Part Ii Submission Date
10-07-2024
Latest Decision Or Authorization Date
19-08-2024
Processing Time Days
40
Number Of Sites
1
Number Of Participants
13

Sites

Site Name
Laiko General Hospital Of Athens
Department Name
First Department Of Internal Medicine
Contact Person Name
Helen Gogas
Contact Person Email
helgogas@gmail.com

Germany

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
03-06-2024
Processing Time Days
18
Number Of Sites
17
Number Of Participants
45

Sites

Site Name
Universitaet Leipzig
Department Name
Department of Dermatology
Contact Person Name
Jan Christoph Simon
Site Name
Universitaetsklinikum Bonn AöR
Department Name
Zentrum für Hauterkrankungen, Klinikfür Dermatoonkologie & Phlebologie
Contact Person Name
Jennifer Landsberg
Contact Person Email
jenny.landsberg@ukbonn.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Nationales Centrum für Tumorerkrankungen
Contact Person Name
Jessica Hassel
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Hauttumorcentrum Charite̒ (HTCC)
Contact Person Name
Max Schlaak
Contact Person Email
max.schlaak@charite.de
Site Name
Universitaetsklinikum Halle (Saale) AöR
Department Name
Poliklinik fuer Dermatologie und Venerologie
Contact Person Name
Johannes Wohlrab

Bulgaria

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
01-07-2024
Processing Time Days
46
Number Of Sites
2
Number Of Participants
7

Sites

Site Name
Medical Center Nadezhda Clinical EOOD
Contact Person Name
Mila Petrova
Contact Person Email
milllapetrova@gmail.com
Site Name
University Specialized Hospital For Active Treatment In Oncology EAD
Department Name
Clinic oof Medical Oncology
Contact Person Name
Assia Konsoulova
Contact Person Email
dr.konsoulova@gmail.com

Czechia

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
29-05-2024
Processing Time Days
13
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Fakultni nemocnice Olomouc
Department Name
Onkologicka klinika
Contact Person Name
Bohuslav Melichar
Contact Person Email
bohuslav.melichar@fnol.cz

Sponsor

Primary sponsor

Full Name
Pfizer Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
Training development and delivery
Name
Parexel International (IRL) Limited
Responsibilities
Medical supply management; study coordination support
Name
Premier Research
Responsibilities
Operational support (listed duty code 6)
Name
PPD Global Central Labs
Responsibilities
Central laboratory services
Name
WCG Clinical Inc.
Responsibilities
Study coordination support services

Third parties

  • {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"product support / listed sponsor duty code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Bulgaria","full_name":"C3i Europe EOOD","duties_or_roles":"Medical escalation and unblinding","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"Medical imaging - central reader","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Training development and delivery","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Medical supply management; other sponsor duties","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Discovery Life Sciences LLC","duties_or_roles":"listed sponsor duty code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Study coordination support services","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"Electronic Clinical Outcomes Assessment (ECOA)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"listed sponsor duty code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"listed sponsor duty code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"France","full_name":"Premier Research","duties_or_roles":"listed sponsor duty code 6","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"Independent oversight committee support, logistics & tech","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Long term storage and biobanking","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
ENCORAFENIB
Active Substance
ENCORAFENIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus 2 (authorised for use in study context listed as SUB177218)
Maximum Dose
450 mg
Investigational Product Name
BINIMETINIB
Active Substance
BINIMETINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus 2 (listed SUB179942)
Maximum Dose
90 mg
Investigational Product Name
KEYTRUDA 25 mg/mL concentrate for solution for infusion
Active Substance
PEMBROLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS
Authorisation Status
Marketing authorisation EU/1/15/1024/002 (authorised biologic PRD4323105)
Maximum Dose
200 mg
Investigational Product Name
Binimetinib placebo
Modality
Other
Authorisation Status
N/A (placebo)
Investigational Product Name
Encorafenib Pacebo
Modality
Other
Authorisation Status
N/A (placebo)
Combination Treatment
Yes

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