IMC-F106C Regimen Versus Nivolumab Regimens in Previously Untreated Advanced Melanoma (PRISM-MEL-301)
- Conditions
- Advanced Melanoma
- Interventions
- Registration Number
- NCT06112314
- Lead Sponsor
- Immunocore Ltd
- Brief Summary
This is a phase 3, randomized, controlled study of brenetafusp (IMC-F106C) plus nivolumab compared to standard nivolumab regimens in HLA-A\*02:01-positive participants with previously untreated advanced melanoma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 680
- Participants must be HLA-A*02:01-positive
- Participants must have histologically confirmed Stage IV or unresectable Stage III melanoma
- Archived or fresh tumor tissue sample that must be confirmed as adequate
- Participants must have measurable disease per RECIST 1.1
- Participant must have BRAF V600 mutation status determined
- Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the study screening date until 5 months after the final dose of study intervention
- Participants with a history of a malignant disease other than those being treated in this study
- Participants with untreated, active, or symptomatic central nervous system (CNS) metastases or carcinomatous meningitis
- Hypersensitivity to IMC-F106C, nivolumab, relatlimab, or any associated excipients
- Participants with clinically significant pulmonary disease or impaired lung function
- Participants with clinically significant cardiac disease or impaired cardiac function
- Participants with active autoimmune disease requiring immunosuppressive treatment
- Participants with any medical condition that is poorly controlled or that would, in the Investigator's or Sponsor's judgment, adversely impact the participant's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results
- Participants who received prior systemic anticancer therapy for unresectable or metastatic melanoma
- Participants with a history of a life-threatening AE related to prior anti-PD-(L)1 or anti-LAG-3
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Brenetafusp Low Dose + Nivolumab Brenetafusp Participants receive brenetafusp Low Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W. Arm A: Brenetafusp Low Dose + Nivolumab Nivolumab Participants receive brenetafusp Low Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W. Arm B: Brenetafusp High Dose + Nivolumab Brenetafusp Participants receive brenetafusp High Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W. Arm B: Brenetafusp High Dose + Nivolumab Nivolumab Participants receive brenetafusp High Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W. Arm C: Nivolumab OR Nivolumab + Relatlimab Nivolumab Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W. Arm C: Nivolumab OR Nivolumab + Relatlimab Nivolumab + Relatlimab Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to ~24 months PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Up to ~36 months OS is the time from randomization to time of death from any cause.
Overall Response Rate (ORR) Up to ~24 months ORR as assessed by BICR according to RECIST 1.1.
Number of Participants Experiencing ≥1 Adverse Event (AE) Up to ~36 months An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur in the study.
Number of Participants Experiencing ≥1 Serious Adverse Event (SAE) Up to ~36 months An SAE is any untoward medical consequence that results in death; requires inpatient hospitalization or prolongs existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or any other important medical event in the opinion of the Investigator.
Number of Participants Experiencing a Dose Interruption, Reduction, or Discontinuation Up to ~24 months The number of participants with a dose interruption, reduction, or discontinuation due to AE will be reported.
Maximum Plasma Concentration (Cmax) of IMC-F106C Day 1 of Weeks 1, 2, and 3: Predose and 0.5 and 4 hours postdose The Cmax of IMC-F106C will be reported.
Incidence of anti-IMC-F106C Antibodies Up to ~24 months The incidence of anti-IMC-F106C antibodies, including neutralizing antibodies, will be reported.
Association between PFS and Intra-Tumor Immune Cells Up to ~24 months The potential association between the effect of IMC-F106C on efficacy and intra-tumor environment will be explored. Intra-tumor environment is estimated as the ratio of CD3+ to CD163+ cells and the correlation with PFS will be estimated by the hazard ratio (+/- 95% CI) from a Cox model. This analysis will be restricted to subjects randomized to receive IMC-F106C.
Trial Locations
- Locations (97)
Fundacao Pio XII - Hospital de Cancer de Barretos - Hospital de Amor
🇧🇷Barretos, Brazil
Centro de Pesquisas Oncologicas (CEPON)
🇧🇷Florianópolis, Brazil
Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) - Hospital Sao Lucas - Centro de Pesquisa Clinica (CPC)
🇧🇷Porto Alegre, Brazil
Instituto do Cancer do Estado de Sao Paulo (ICESP)
🇧🇷São Paulo, Brazil
University Hospital Tsaritsa Yoanna (ISUL) (Queen Giovanna University Hospital)
🇧🇬Sofia, Bulgaria
Semmelweis Egyetem Általános Orvostudományi Kar
🇭🇺Budapest, Hungary
Humanitas Gavazzeni (Cliniche Gavazzeni S.p.A)
🇮🇹Bergamo, Italy
Complejo Hospitalario Universitario A Coruna (CHUAC)
🇪🇸A Coruña, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Centro Integral Oncologico Clara Campal (CIOCC)
🇪🇸Madrid, Spain
Karolinska Universitetssjukhuset
🇸🇪Stockholm, Sweden
Kanser Enstitusu (Hacettepe University Cancer Institute)
🇹🇷Altındağ, Turkey
T.C. Saglik Bakanligi - SBU Gulhane Egitim ve Arastirma Hastanesi
🇹🇷Ankara, Turkey
Ankara Bilkent City Hospital, Oncology Department
🇹🇷Çankaya, Turkey
Sarah Cannon Research Institute (SCRI) - London (SCRI-UK)
🇬🇧London, United Kingdom
The Angeles Clinic and Research Institute- West Los Angeles
🇺🇸Los Angeles, California, United States
ESC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UCLA Hematology/Oncology
🇺🇸Los Angeles, California, United States
University of Colorado, Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Northwestern University - Robert H. Lurie Comprehensive Cancer Center - NMDTI
🇺🇸Chicago, Illinois, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Northwell Health Cancer Institute
🇺🇸Lake Success, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Prisma Health Cancer Institute
🇺🇸Greenville, South Carolina, United States
Swedish Medical Center - Swedish Cancer Institute (SCI) - First Hill Campus
🇺🇸Seattle, Washington, United States
Sanatorio Finochietto
🇦🇷Caba, Buenos Aires, Argentina
Clínica Adventista Belgrano - Sector Investigación
🇦🇷Caba, Buenos Aires, Argentina
Instituto Alexander Fleming
🇦🇷Caba, Argentina
Clinica Viedma
🇦🇷Viedma, Argentina
Gallipoli Medical Research Foundation (Greenslopes Private Hospital)
🇦🇺Greenslopes, Queensland, Australia
Austin Hospital
🇦🇺Heidelberg, Australia
Peter MacCallum Cancer Centre
🇦🇺North Melbourne, Australia
University of Sydney - Melanoma Institute Australia (MIA) - The Poche Centre
🇦🇺Wollstonecraft, Australia
The University of Queensland (UQ) - Princess Alexandra Hospital (PAH)
🇦🇺Woolloongabba, Australia
Universitätsklinikum St. Pölten
🇦🇹Pölten, Austria
Paracelsus Medizinischen Privatuniversitaet - SALK - Universitaetsklinik fuer Dermatologie - EB-Haus Austria
🇦🇹Salzburg, Austria
Uni Hospital
🇧🇬Panagyurishte, Bulgaria
Complex Oncology Center - Plovdiv Ltd.
🇧🇬Plovdiv, Bulgaria
Regina Life Clinic
🇧🇬Sofia, Bulgaria
Sanatorium Profesora Arenbergera
🇨🇿Praha, Czechia
Kobenhavns Universitet - Herlev Hospital (Amtssygehuset i Herlev)
🇩🇰Herlev, Denmark
Hôpital de la Timone
🇫🇷Marseille, Cedex, France
Oncopole Claudius Regaud- Institut Universitaire du Cancer de Toulouse
🇫🇷Toulouse, Cedex, France
Assistance Publique-Hopitaux de Paris (AP-HP) - Hopitaux Universitaires Paris Seine-Saint-Denis - Hopital Avicenne
🇫🇷Bobigny, France
Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Ambroise-Pare
🇫🇷Boulogne-Billancourt, France
CHU de Dijon Bourgogne - Hôpital François Mitterrand
🇫🇷Dijon, France
Centre Hospitalier Universitaire de Lille (CHU Lille)-Hopital Claude Huriez
🇫🇷Lille, France
Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu
🇫🇷Nantes, France
Hospital Saint Louis
🇫🇷Paris, France
Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
🇫🇷Pierre-Benite, France
Centre Hospitalier Universitaire de Rouen (CHU de Rouen) - Hopital Charles-Nicolle
🇫🇷Rouen, France
Hopital Robert Debre
🇫🇷Valence, France
Institut Gustave Roussy (IGR) Service de Dermatolgie
🇫🇷Villejuif, France
Charite-Universitaetsmedizin Berlin - Campus Charite Mitte (CCM) - Klinik fuer Dermatologie Venerologie und Allergologie - Hauttumorcentrum Charite (HTCC)
🇩🇪Berlin, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
University of Hamburg
🇩🇪Hamburg, Germany
Elbe Kliniken Stade - Hautkrebszentrum Buxtehude
🇩🇪Hamburg, Germany
Universitaetsklinikum Heidelberg (UKHD) - Hautklinik
🇩🇪Heidelberg, Germany
Universitaetsklinikum Leipzig - Klinik fuer Dermatologie, Venerologie und Allergologie
🇩🇪Leipzig, Germany
Johannes Wesling Klinikum Minden
🇩🇪Minden, Germany
Universitaetsklinikum Tuebingen (UKT) - Zentrum fuer Dermatoonkologie - Hautklinik
🇩🇪Tübingen, Germany
Universitaetsklinikum Wuerzburg - Klinik und Poliklinik fuer Dermatologie Venerologie und Allergologie
🇩🇪Würzburg, Germany
Pecsi Tudomanyegyetem (PTE) (University of Pecs)
🇭🇺Pécs, Hungary
Istituto Tumori Giovanni Paolo II - Ospedale Oncologico di Bari
🇮🇹Bari, Italy
IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori "Dino Amadori" Srl (IRST)
🇮🇹Meldola, Italy
Istituto Europeo di Oncologia (IEO) (European Institute of Oncology)
🇮🇹Milan, Italy
Istituto Nazionale Tumori (INT) "Fondazione G. Pascale" di Napoli
🇮🇹Napoli, Italy
Istituto Oncologico Veneto (IOV) IRCCS
🇮🇹Padova, Italy
Azienda Sanitaria Locale di Biella (ASL BI) - Ospedale degli Infermi
🇮🇹Ponderano, Italy
" Azienda Ospedaliera Universitaria Senese - Policlinico Santa Maria Alle Scotte - Clinica Immunoterapia Oncologica"
🇮🇹Siena, Italy
Centrum Onkologii im. Prof. Franciszka Łukaszczyka
🇵🇱Bydgoszcz, Poland
Klinika Onkologii i Radioterapii Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Centrum Medyczne Pratia Poznań - Skorzewo
🇵🇱Skorzewo, Poland
Klinika Nowotworów Tkanek Miękkich, Kości i Czerniaków
🇵🇱Warszawa, Poland
Sf Nectarie Oncology Center
🇷🇴Craiova, Romania
Universidad de Murcia - Hospital Universitario Virgen de la Arrixaca (HUVA)
🇪🇸El Palmar, Murcia, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Dexeus
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Virgen de las Nieves (HUVN)
🇪🇸Granada, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Macarena
🇪🇸Seville, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Sahlgrenska Akademin - Institutionen for Kliniska Vetenskaper (Institute of Clinical Sciences)
🇸🇪Göteborg, Sweden
Uppsala Universitet - Akademiska Sjukhuset (Uppsala University Hospital)
🇸🇪Uppsala, Sweden
UniversitaetsSpital Zuerich - Dermatologische Klinik
🇨🇭Zurich, Switzerland
Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospital (AH) - Oncology Centre
🇬🇧Cambridge, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Royal Marsden Hospital - Sutton
🇬🇧Surrey Quays, United Kingdom