A Phase 3 Randomized, Controlled Study of IMC-F106C Plus Nivolumab Versus Nivolumab Regimens in HLA-A*02:01-Positive Participants With Previously Untreated Advanced Melanoma (PRISM-MEL-301

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: Immunocore Ltd (industry)

Phase: 3

Start date: June 5, 2024

Planned enrollment: 680

Trial ID: NCT06112314
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

chevron Show for: Brenetafusp (IMC-F106C, PRAME-A02)

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Goal: To determine whether adding the PRAME‑targeted TCR/CD3 bispecific brenetafusp (IMC‑F106C) to nivolumab improves outcomes versus contemporary PD‑1–based regimens (nivolumab or nivolumab plus relatlimab) in previously untreated, HLA‑A*02:01–positive advanced melanoma.

Patients: Adults with histologically confirmed unresectable stage III or stage IV melanoma, HLA‑A*02:01–positive, measurable disease by RECIST 1.1, ECOG 0–1, and known BRAF V600 status. Key exclusions include prior systemic therapy for advanced melanoma, active or untreated CNS metastases, clinically significant pulmonary or cardiac disease, active autoimmune disease requiring immunosuppression, and hypersensitivity to study drugs.

Design: Global, randomized, controlled, phase 3 study with parallel arms. Allocation is randomized; dose selection between two brenetafusp dose levels will occur within the experimental arms. Planned enrollment ~680 participants.

Treatments: Two experimental regimens: brenetafusp plus nivolumab. Brenetafusp is an investigational, off‑the‑shelf, soluble T‑cell receptor–CD3 bispecific (ImmTAC) that binds an HLA‑A*02:01‑restricted PRAME peptide on tumor cells and CD3 on T cells to redirect polyclonal T‑cell cytotoxicity. Early phase melanoma data show manageable safety with predominantly grade 1–2 cytokine release syndrome and rash, disease control rates around 56–61% and modest ORR as monotherapy post‑checkpoint; combination with PD‑1 blockade has shown preliminary disease control including partial responses. The control arm receives standard nivolumab 480 mg every 4 weeks or fixed‑dose nivolumab 480 mg plus relatlimab 160 mg every 4 weeks, consistent with approved PD‑1 or PD‑1/LAG‑3 regimens. Dosing schedules: brenetafusp weekly for 13 weeks, then every 2 weeks through Week 51, then every 4 weeks thereafter; nivolumab every 4 weeks in all arms.

Outcomes: Primary endpoint: progression‑free survival by blinded independent central review per RECIST 1.1. Key secondary endpoints include overall survival, overall response rate by BICR, safety (AEs, SAEs, and treatment modifications), pharmacokinetics (IMC‑F106C Cmax), anti‑drug antibodies, exploratory biomarker associations between intra‑tumoral immune contexture (CD3+/CD163+ ratio) and PFS in the IMC‑F106C arms, and health‑related quality of life. Follow‑up for efficacy up to approximately 45 months for PFS/response and 57 months for OS and safety.

Burden on patient: Moderate. Visit intensity is front‑loaded with weekly brenetafusp infusions for 13 weeks, then biweekly through one year before moving to every 4 weeks; control arm visits are every 4 weeks. Expect baseline and on‑study tumor assessments per RECIST at standard intervals, additional blood draws for safety labs, pharmacokinetics on early cycles (predose and multiple postdose timepoints during Weeks 1–3), and immunogenicity sampling. Archival or fresh tumor tissue is required, and exploratory biomarker work may necessitate adequate tissue, with possible optional biopsies. Travel and chair time are greater in the experimental arms during the first year relative to standard PD‑1 regimens, but otherwise procedures align with typical phase 3 oncology standards, without inpatient requirements anticipated for routine care.

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Prague, 110 00, Czechia

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Elbe Kliniken Stade - Hautkrebszentrum Buxtehude

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University of Hamburg

Hamburg, 20246, Germany

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Berlin, 10115, Germany

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Dresden, 01307, Germany

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Heidelberg, 69120, Germany

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Budapest, 1085, Hungary

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Szegedi Tudomanyegyetem (University of Szeged)

Szeged, 6720, Hungary

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Bergamo, 24125, Italy

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Milan, 20141, Italy

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Milan, 20133, Italy

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Roma, 00128, Italy

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Roma, 0168, Italy

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Siena, 53100, Italy

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Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino

Torino, 10126, Italy

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Centrum Medyczne Pratia Poznań - Skorzewo

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Klinika Nowotworów Tkanek Miękkich, Kości i Czerniaków

Warsaw, 02-781, Poland

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Centrum Onkologii im. Prof. Franciszka Łukaszczyka

Bydgoszcz, 85796, Poland

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Victoria Hospital (Centrul de oncologie Euroclinic SRL) (Centrul De Oncologie Medicala) (Euroclinic Onchology Center)

Iași, 700106, Romania

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Sf Nectarie Oncology Center

Craiova, 200542, Romania

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Universidad de Cantabria (UC) - Hospital Universitario Marques de Valdecilla (HUMV)

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Valencia, 46014, Spain

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Valencia, 46026, Spain

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Madrid, 28009, Spain

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Granada, 18014, Spain

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Madrid, 28034, Spain

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Madrid, 28041, Spain

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Hospital Universitario La Paz

Madrid, 28046, Spain

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Centro Integral Oncologico Clara Campal (CIOCC)

Madrid, 28050, Spain

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Hospital Regional Universitario de Malaga

Málaga, 29016, Spain

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Pamplona, 31008, Spain

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Hospital Universitario Virgen Macarena

Seville, 41009, Spain

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Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

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Instituto de Investigacion Sanitaria (INCLIVA) (Institute of Health Research Hospital Clinic of Valencia)

Valencia, 46010, Spain

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Karolinska Universitetssjukhuset

Stockholm, 171 76, Sweden

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Sahlgrenska Akademin - Institutionen for Kliniska Vetenskaper (Institute of Clinical Sciences)

Gothenburg, SE41345, Sweden

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Lanssjukhuset Ryhov - Onkologiska Kliniken

Jönköping, 553 05, Sweden

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Skanes Universitetssjukhus - Lund - Onkologiska Klinik

Lund, 22185, Sweden

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Uppsala Universitet - Akademiska Sjukhuset (Uppsala University Hospital)

Uppsala, SE75185, Sweden

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UniversitaetsSpital Zuerich - Dermatologische Klinik

Zurich, 8901, Switzerland

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Status: Recruiting

Memorial Saglik Grubu - Memorial Ankara Hastanesi

Çankaya, Ankara, 06520, Turkey (Türkiye)

[email protected] / 0506 752 12 75

Status: Recruiting

Medical Park Hastaneler Grubu - I.A.U. VM Medical Park Florya

Antalya, Campus, 07070, Turkey (Türkiye)

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Medical Park Gaziantep Hastanesi

Şehitkamil, Gaziantep, 27584, Turkey (Türkiye)

[email protected] / 0555 241 46 87

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Memorial Saglik Grubu - Memorial Bahcelievler Hastanesi

Bahçelievler, Istanbul, 34180, Turkey (Türkiye)

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Ege Universitesi Tip Fakultesi (Ege University Faculty of Medicine)

Bornova, İzmir, 35100, Turkey (Türkiye)

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Status: Recruiting

Izmir Ekonomi Universitesi Medikal Point Hastanesi

Cordaleo, İzmir, 35575, Turkey (Türkiye)

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Status: Recruiting

Kanser Enstitusu (Hacettepe University Cancer Institute)

Altındağ, 6230, Turkey (Türkiye)

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Status: Recruiting

Medical Park Seyhan Hastanesi

Seyhan, 1140, Turkey (Türkiye)

[email protected] / +90 533 361 69 39

Status: Recruiting

T.C. Saglik Bakanligi - Ankara Etlik sehir Hastanesi

Yenimahalle, 06170, Turkey (Türkiye)

[email protected] / +90 536 640 10 20

Status: Recruiting

Ondokuz Mayis Universitesi (OMU) - Tip Facultesi

Samsun, 55270, Turkey (Türkiye)

[email protected] / 0532 599 28 25

Status: Recruiting

Inonu Universitesi - Turgut Ozal Tip Merkezi

Malatya, 44280, Turkey (Türkiye)

[email protected] / 0533 572 01 75

Status: Recruiting

Ankara Bilkent City Hospital, Oncology Department

Çankaya, 6800, Turkey (Türkiye)

No email / No phone

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T.C. Saglik Bakanligi - SBU Gulhane Egitim ve Arastirma Hastanesi

Ankara, 6100, Turkey (Türkiye)

[email protected] / +90 536 640 10 20

Status: Recruiting

Sarah Cannon Research Institute (SCRI) - London (SCRI-UK)

London, W1G 6AD, United Kingdom

[email protected] / 0203 219 5200

Status: Recruiting

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, L78YA, United Kingdom

[email protected] / 01515565435

Status: Recruiting

The Christie NHS Foundation Trust

Manchester, M204BX, United Kingdom

No email / No phone

Status: Recruiting

Royal Marsden Hospital - Sutton

Surrey Quays, SM2 5PT, United Kingdom

No email / No phone

Status: Recruiting

Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospital (AH) - Oncology Centre

Cambridge, CB20QQ, United Kingdom

No email / No phone

Status: Recruiting

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

[email protected] / 0141 301 7043

Status: Recruiting

University of Arizona

Tucson, Arizona, 85720, United States

[email protected] / 520-621-2029

Status: Recruiting

The Angeles Clinic and Research Institute- West Los Angeles

Los Angeles, California, 90025, United States

[email protected] / 310-231-2181

Status: Recruiting

University of California - San Diego

La Jolla, California, 92093-0698, United States

[email protected] / 858-822-6575

Status: Recruiting

ESC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

[email protected] / 323-865-3935

Status: Recruiting

Saint John's Health Center - John Wayne Cancer Institute (JWCI)

Santa Monica, California, 90404, United States

[email protected] / 310-582-7457

Status: Recruiting

Stanford Cancer Institute - Stanford Cancer Center Palo Alto

Palo Alto, California, 94304, United States

[email protected] / 650-736-6425

Status: Recruiting

UCLA Hematology/Oncology

Los Angeles, California, 90095, United States

[email protected] / 310-794-3266

Status: Recruiting

University of Colorado, Anschutz Medical Campus

Aurora, Colorado, 80045, United States

[email protected] / 720-848-9381

Status: Recruiting

UConn Health-Farmington (University of Connecticut Health Center (UCHC))

Farmington, Connecticut, 06030-2205, United States

No email / No phone

Status: Recruiting

Georgetown University

Washington D.C., District of Columbia, 20007, United States

No email / No phone

Status: Recruiting

University of Miami Health System-Sylvester Comprehensive Cancer Center-Miami

Miami, Florida, 33136, United States

[email protected] / No phone

Status: Recruiting

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

[email protected] / 904-953-5323

Status: Recruiting

Northwestern University - Robert H. Lurie Comprehensive Cancer Center - NMDTI

Chicago, Illinois, 60611, United States

No email / No phone

Status: Recruiting

The University of Kansas Cancer Center (KUCC) - Westwood

Westwood, Kansas, 66205, United States

[email protected] / 913-945-7552

Status: Recruiting

St. Elizabeth Healthcare - Edgewood

Edgewood, Kentucky, 41017, United States

[email protected] / 859-301-4243

Status: Recruiting

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

[email protected] / 617-632-6704

Status: Recruiting

Washington University School of Medicine

St Louis, Missouri, 63110, United States

No email / No phone

Status: Completed

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

[email protected] / 551-996-1777

Status: Recruiting

Columbia University Medical Center

New York, New York, 10032, United States

No email / No phone

Status: Completed

Northwell Health Cancer Institute

Lake Success, New York, 11042, United States

[email protected] / No phone

Status: Recruiting

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

[email protected] / 267-414-8820

Status: Recruiting

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

[email protected] / 412-623-3544

Status: Recruiting

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

[email protected] / No phone

Status: Recruiting

Spartanburg Regional Healthcare System - Spartanburg Medical Center (SMC)

Spartanburg, South Carolina, 29303, United States

[email protected] / 864-530-6554

Status: Recruiting

Sarah Cannon Research Institute: USA/TN

Nashville, Tennessee, 37203, United States

No email / No phone

Status: Recruiting

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

[email protected] / 801-213-8486

Status: Recruiting

UVA Health-UVA Emily Couric Clinical Cancer Center

Charlottesville, Virginia, 22903, United States

[email protected] / No phone

Status: Recruiting

Swedish Medical Center - Swedish Cancer Institute (SCI) - First Hill Campus

Seattle, Washington, 98104, United States

[email protected] / 206-215-3125

Status: Recruiting

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