JOURNAL ONKOLOGIE – STUDIE

PORTSIDE

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

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05926960

Studienbeginn:
Juni 2023

Letztes Update:
23.04.2024

Wirkstoff:
Encorafenib, Binimetinib, Pembrolizumab, Ipilimumab, Nivolumab

Indikation (Clinical Trials):
Melanoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Pfizer

Collaborator:
Merck Sharpe & Dohme LLC

Studienleiter

Pfizer CT.gov Call Center
Study Director
Pfizer

Kontakt

Pfizer CT.gov Call Center
Kontakt:
Phone: 1-800-718-1021
E-Mail: ClinicalTrials.gov_Inquiries@pfizer.com» Kontaktdaten anzeigen

Studienlocations
(3 von 63)

Universitaetsklinikum Heidelberg
69120 Heidelberg
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps

Universitaetsklinikum Tuebingen
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Pankreaskarzinomzentrum Universitätsklinikum Regensburg
Franz-Josef-Strauß-Allee 11
93053 Regensburg
DeutschlandNoch nicht rekrutierend» Google-Maps

Elbe Kliniken Stade-Buxtehude, Klinikum Buxtehude
21614 Buxtehude
(Niedersachsen)
GermanyNoch nicht rekrutierend» Google-Maps

Leberkrebszentrum Medizinische Hochschule Hannover
Carl-Neuberg-Straße 1
30625 Hannover
DeutschlandRekrutierend» Google-Maps

Universitaetsklinikum Essen
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Fachklinik Hornheide
48157 Münster
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Universitätsmedizin Johannes Gutenberg Universität Mainz
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps

Gynäkologisches Tumorzentrum am Universitätsklinikum Leipzig
4103 Leipzig
DeutschlandNoch nicht rekrutierend» Google-Maps

Darmkrebszentrum am Universitätsklinikum Schleswig-Holstein, Campus Lübeck
Ratzeburger Allee 160
23562 Lübeck
DeutschlandRekrutierend» Google-Maps

Lungenkrebszentrum Helios Klinikum Erfurt
Nordhäuser Straße 74
99089 Erfurt
(Thüringen)
DeutschlandNoch nicht rekrutierend» Google-Maps

SRH Wald-Klinikum Gera
07548 Gera
(Thüringen)
GermanyNoch nicht rekrutierend» Google-Maps

Klinikum Bremen-Ost
28325 Bremen
GermanyNoch nicht rekrutierend» Google-Maps

Fakultni nemocnice Hradec Kralove
500 05 Hradec Kralove
CzechiaNoch nicht rekrutierend» Google-Maps

Fakultni nemocnice Ostrava
708 52 Ostrava
CzechiaNoch nicht rekrutierend» Google-Maps

Fakultni nemocnice Olomouc
779 00 Olomouc
CzechiaNoch nicht rekrutierend» Google-Maps

Fakultni nemocnice Bulovka
180 81 Prague
CzechiaNoch nicht rekrutierend» Google-Maps

Vseobecna fakultni nemocnice v Praze
12808 Praha 2
CzechiaNoch nicht rekrutierend» Google-Maps

Istituto Nazionale Tumori Regina Elena
00144 Rome
ItalyRekrutierend» Google-Maps

A.O.U. Policlinico Paolo Giaccone
90127 Palermo
ItalyRekrutierend» Google-Maps

Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
10060 Candiolo
ItalyRekrutierend» Google-Maps

Azienda Ospedaliero Universitaria Senese
53100 Siena
ItalyRekrutierend» Google-Maps

AO Santa Maria della Misericordia
06132 Perugia
ItalyRekrutierend» Google-Maps

Istituto Oncologico Veneto IRCCS
35128 Padova
ItalyRekrutierend» Google-Maps

Ospedale San Martino
16132 Genova
ItalyNoch nicht rekrutierend» Google-Maps

Istituto Europeo di Oncologia IRCCS
20141 Milano
ItalyRekrutierend» Google-Maps

Istituto Nazionale Tumori IRCCS Fondazione Pascale
80131 Napoli
ItalyRekrutierend» Google-Maps

Uniwersyteckie Centrum Kliniczne Klinika Chirurgii Onkologicznej, Transplantacyjnej i Ogólnej
80-214 Gdansk
PolandRekrutierend» Google-Maps

Pratia MCM Krakow
30-727 Krakow
PolandRekrutierend» Google-Maps

Samodzielny Publiczny Zakład Opieki Zdrowotnej MSWiA z Warmińsko - Mazurskim Centrum Onkologii
10-228 Olsztyn
PolandRekrutierend» Google-Maps

Uniwersytecki Szpital Kliniczny w Poznaniu
60-780 Poznan
PolandRekrutierend» Google-Maps

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
02-781 Warszawa
PolandNoch nicht rekrutierend» Google-Maps

Fakultna Nemocnica s Poliklinikou F. D. Roosevelta Banska Bystrica
975 17 Banska Bystrica
SlovakiaNoch nicht rekrutierend» Google-Maps

Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
975 17 Banska Bystrica
SlovakiaNoch nicht rekrutierend» Google-Maps

Fakultna nemocnica s poliklinikou F.D. Roosevelta
975 17 Banska Bystrica
SlovakiaNoch nicht rekrutierend» Google-Maps

Narodny onkologicky ustav
833 10 Bratislava
SlovakiaRekrutierend» Google-Maps

Euromedix, a.s.
851 07 Bratislava
SlovakiaNoch nicht rekrutierend» Google-Maps

Neovizia, s.r.o.
85101 Bratislava
SlovakiaRekrutierend» Google-Maps

Institut nuklearnej a molekularnej mediciny
042 53 Kosice
SlovakiaNoch nicht rekrutierend» Google-Maps

Martinske Biopticke centrum, s.r.o.
036 01 Martin
SlovakiaNoch nicht rekrutierend» Google-Maps

DERMATOP s.r.o., MUDr. Frantisek Perutka
958 01 Partizanske
SlovakiaNoch nicht rekrutierend» Google-Maps

Nemocnica na okraji mesta, n.o.
95801 Partizanske
SlovakiaNoch nicht rekrutierend» Google-Maps

KARDIO, s.r.o.
058 01 Poprad
SlovakiaNoch nicht rekrutierend» Google-Maps

MR Poprad s.r.o., Pracovisko magnetickej rezonancie
058 01 Poprad
SlovakiaNoch nicht rekrutierend» Google-Maps

Nemocnica Poprad, a.s., Dermatovenerolgicka ambulancia
058 01 Poprad
SlovakiaNoch nicht rekrutierend» Google-Maps

POKO Poprad, s.r.o., Ambulancia klinickej onkologie
058 01 Poprad
SlovakiaNoch nicht rekrutierend» Google-Maps

Nemocnica Poprad, a.s.
05801 Poprad
SlovakiaNoch nicht rekrutierend» Google-Maps

Ocne centrum Sokolik, s.r.o.
91101 Trencin
SlovakiaNoch nicht rekrutierend» Google-Maps

H.R.U Málaga - Hospital General
29010 Malaga
SpainNoch nicht rekrutierend» Google-Maps

Hospital Germans Trias i Pujol
08916 Badalona
SpainRekrutierend» Google-Maps

Hospital Universitari Vall d'Hebron
08035 Barcelona
SpainRekrutierend» Google-Maps

Institut Català d'Oncologia - L'Hospitalet
08908 L'Hospitalet de Llobregat
SpainRekrutierend» Google-Maps

Hospital General Universitario de Valencia
46014 Valencia
SpainRekrutierend» Google-Maps

Hospital General Universitario de Alicante
03010 Alicante
SpainRekrutierend» Google-Maps

Hospital Clínic de Barcelona
08036 Barcelona
SpainNoch nicht rekrutierend» Google-Maps

Hospital General Universitario Gregorio Marañon
28007 Madrid
SpainRekrutierend» Google-Maps

Hospital Universitario 12 de Octubre
28041 Madrid
SpainRekrutierend» Google-Maps

Hospital Universitario Virgen Macarena
41009 Sevilla
SpainNoch nicht rekrutierend» Google-Maps

Hospital Universitario Miguel Servet
50009 Zaragoza
SpainRekrutierend» Google-Maps

Addenbrooke's Hospital
CB2 0QQ Cambridge
United KingdomNoch nicht rekrutierend» Google-Maps

Royal Marsden Hospital (Chelsea)
SW3 6JJ London
United KingdomNoch nicht rekrutierend» Google-Maps

Royal Marsden Hospital (Sutton)
SM2 5PT London
United KingdomNoch nicht rekrutierend» Google-Maps

City Hospital, Nottingham University Hospitals NHS Trust
NG5 1PB Nottingham
United KingdomNoch nicht rekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

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 Frame - 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 outcome:

1. Progression Free Survival in each treatment arm (Time Frame - 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))

2. Overall Survival in each treatment arm (Time Frame - 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))

3. Duration of Response (CR or PR) in each treatment arm (Time Frame - 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))

4. Disease Control Rate (proportion of participants with a confirmed best overall response of CR, PR or SD) in each treatment arm (Time Frame - 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))

5. Time to Response (CR or PR) (Time Frame - 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))

6. Progression Free Survival 2 in each treatment arm (Time Frame - 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))

7. Incidence and severity of Adverse Events (AEs) and changes in clinical laboratory parameters, vital signs, and cardiac assessments. (Time Frame - Time from first dose of study intervention through 28 days after the last dose of study intervention):
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).

8. Patient Reported Outcomes using EORTC QLQ-C30 questionnaires in each treatment arm (Time Frame - 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)):
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

9. Patient Reported Outcomes using EuroQOL EQ-5D-5L questionnaires in each treatment arm (Time Frame - 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)):
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).

10. BRAF V600E/K Variant Allele Frequency and/or overall mean Variant Allele Frequency from circulating tumour DNA analysis in each treatment arm (Time Frame - Change from baseline, Day 1 of Cycle 2 (after 3 weeks), and End of Treatment (assessed up to approximately 48 months))

Studien-Arme

Experimental: Triplet
encorafenib and binimetinib in combination with pembrolizumab
Active Comparator: Doublet
ipilimumab and nivolumab

Geprüfte Regime

encorafenib (BRAFTOVI):
encorafenib
binimetinib (MEKTOVI):
binimetinib
pembrolizumab (KEYTRUDA®):
pembrolizumab
ipilimumab (YERVOY):
ipilimumab
nivolumab (OPDIVO):
nivolumab

Quelle: ClinicalTrials.gov

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

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