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NCT05727904PHASE3Recruiting

Study to Investigate Lifileucel Regimen Plus Pembrolizumab Compared With Pembrolizumab Alone in Participants With Untreated Advanced Melanoma.

Iovance Biotherapeutics, Inc.

Start Date

3/30/2023

Completion Date

3/1/2030

Summary

This is a Phase 3, multicenter, open-label, randomized, parallel group, treatment study to assess the efficacy and safety of lifileucel in combination with pembrolizumab compared with pembrolizumab alone in participants with untreated, unresectable or metastatic melanoma. Participants randomized to the pembrolizumab monotherapy arm who subsequently have a blinded independent central review- verified confirmed progressive disease (PD) will be offered lifileucel monotherapy in an optional crossover period.

Detailed Description

The study will enroll participants with unresectable or metastatic melanoma (Stage IIIC, IIID, or IV per the American Joint Committee on Cancer \[AJCC\] staging system) who have had no prior therapy for metastatic disease. Previous adjuvant/neoadjuvant therapy with a single line of protooncogene B-Raf (BRAF) inhibitor with or without a mitogen-activated protein kinase (MEK) inhibitor, PD-1 inhibitor, or cytotoxic T-lymphocyte-associated antigen-4 \[CTLA-4\] inhibitor is allowed, provided such treatment was completed ≥6 months before progression to metastatic disease.

Eligibility Criteria

Age Range: 18 years to 70 years

Inclusion Criteria: 1. Participant has a histologically or pathologically confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma. 2. In the investigator's assessment, the participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of \> 6 months. 3. Participant is assessed as having at least one resectable lesion (or aggregate lesions) for lifileucel generation. 4. Participant must have at least one measurable disease as defined by RECIST 1.1 following tumor resection. 5. Participants must have adequate organ function. 6. Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control. 7. Participants who are \> 70 years of age may be allowed to enroll after the investigator discusses with the medical monitor. Exclusion Criteria: 1. Participant has melanoma of uveal/ocular origin. 2. Participant has symptomatic untreated brain metastases. 3. Participant received more than 1 prior line of therapy. 4. Participant received prior therapy for metastatic disease 5. Participants with a BRAF V600 mutation-positive tumor received prior adjuvant/neoadjuvant ICI therapy only 6. Participant has an active medical illness(es) that, in the opinion of the investigator, would pose increased risks for study participation, such as systemic infections; seizure disorders; coagulation disorders; or other active major medical illnesses of the cardiovascular, respiratory, or immune systems. 7. Participant has any form of primary or acquired immunodeficiency (eg, SCID or AIDS). 8. Participant had another primary malignancy within the previous 3 years (except for those that do not require treatment or were curatively treated \>1 year ago, and in the judgment of the investigator do not pose a significant risk of recurrence.) 9. Participant has a history of allogeneic cell or organ transplant. Other protocol defined inclusion/exclusion criteria could apply.

Interventions

BIOLOGICAL

Lifileucel plus Pembrolizumab

BIOLOGICAL

Pembrolizumab with Optional Crossover Period

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Conditions

Metastatic MelanomaUnresectable MelanomaMelanoma

Locations

University of Alabama at Birmingham: The Kirklin Clinic

Birmingham, Alabama 35233

United States

City of Hope

Duarte, California 91010

United States

USC Norris Comprehensive Cancer Center

Los Angeles, California 90007

United States

California Pacific Medical Center

San Francisco, California 94107

United States

University of Colorado Cancer Center

Aurora, Colorado 80045

United States

Orlando Health Cancer Institute

Orlando, Florida 32806

United States

University of Illinois Hospital & Health Sciences System

Chicago, Illinois 60612

United States

University of Kansas

Kansas City, Kansas 66205

United States

University of Louisville - James Graham Brown Cancer Center

Louisville, Kentucky 40202

United States

National Cancer Institute

Bethesda, Maryland 20814

United States

Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center

Detroit, Michigan 48201

United States

Henry Ford Health

Detroit, Michigan 48202

United States

University of Minnesota

Minneapolis, Minnesota 55455

United States

Dartmouth-Hitchcock Medical Center (DHMC) - Norris Cotton Cancer Center

Lebanon, New Hampshire 03756

United States

MD Anderson Cancer Center at Cooper

Camden, New Jersey 08103

United States

Oncology Hematology Care

Cincinnati, Ohio 45226

United States

Ohio State University

Columbus, Ohio 43201

United States

St. Luke's Cancer Center - Anderson

Easton, Pennsylvania 18045

United States

Allegheny Health Network

Pittsburgh, Pennsylvania 15224

United States

Baptist Cancer Center

Bartlett, Tennessee 37920

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

Intermountain Health

Salt Lake City, Utah 84112

United States

Virginia Commonwealth University

Richmond, Virginia 23298

United States

Swedish Cancer Institute

Edmonds, Washington 98026

United States

Greenslopes Private Hospital

Greenslopes, Queensland 4120

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

Fiona Stanley Hospital

Murdoch, Western Australia 6150

Australia

Flinders Medical Centre

Bedford Park, 5042

Australia

Westmead Hospital

Westmead, NSW 2145

Australia

Universitair Ziekenhuis Brussel - Oncologisch Centrum

Jette,

Belgium

Centre hospitalier de l'Université de Montréal

Montreal, Quebec H2L 4M1

Canada

Princess Margaret Cancer Centre

Toronto, M5G

Canada

Helsinki University Hospital Comprehensive Cancer Center

Helsinki, Finland 290

Finland

Institut Paoli Calmettes

Marseille, 13009

France

Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu

Nantes, 44093

France

Hopital Saint Louis

Paris, 75475

France

Charité - Universitätsmedizin Berlin

Berlin, Germany 13353

Germany

Universitätsklinikum Carl Gustav Carus

Dresden, 1307

Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20251

Germany

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, 23562

Germany

Klinikum Rechts der Isar der Technischen Universität München

Munich, 81675

Germany

Hadassah Medical Center

Jerusalem,

Israel

Sheba Medical Center

Ramat Gan, 52621

Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906

Israel

Istituto Romagnolo per lo Studio dei Tumori

Meldola, Forlì-Cesena 47014

Italy

Centro di Riferimento Oncologico IRCCS

Aviano, Friuli Venezia Giulia 33081

Italy

Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale

Naples, Napoli 80131

Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany 56100

Italy

Istituto Europeo Di Oncologia

Milan, 20139

Italy

Azienda Ospedaliera Universitaria Senese

Siena,

Italy

Nederlands Kanker Instituut

Amsterdam, 1066 CX

Netherlands

National Cancer Centre Singapore

Singapore, Singapore 168582

Singapore

Bundang Medical Center - CHA University

Seongnam-si, Gyeonggi-do

South Korea

Samsung Medical Center

Seoul, South Korea 135-890

South Korea

Korea University Anam Hospital

Seoul, 2841

South Korea

Seoul National University Hospital

Seoul, 3080

South Korea

Severance Hospital, Yonsei University Health System

Seoul, 3722

South Korea

Hospital Universitario Marques de Valdecilla

Santander, Cantabria 39008

Spain

Hospital Regional Universitario de Malaga - Hospital General

Málaga, Málaga 29016

Spain

Institut Català d'Oncologia (ICO)

Barcelona, Spain 8908

Spain

HM Centro Integral Oncologico Clara Campal

Madrid, Spain 28050

Spain

Instituto Oncologico Rosell

Barcelona, 08028

Spain

Hospital Universitari Vall dHebron

Barcelona, 08035

Spain

Hospital Clinic de Barcelona

Barcelona, 8036

Spain

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, 8908

Spain

Hospital General Universitario Gregorio Maranon

Madrid, 28007

Spain

Hospital 12 de Octubre

Madrid, 28041

Spain

Hospital Universitario Madrid Sanchinarro - CIOCC

Madrid, 28050

Spain

Hospital Universitario Quirónsalud Madrid

Madrid, 28223

Spain

Hospital Universitario Ramon y Cajal

Madrid,

Spain

Clínica Universitaria de Navarra

Pamplona, 31008

Spain

Hospital Universitario Virgen Macarena

Seville, 41009

Spain

Consorcio Hospital General Universitario de Valencia

Valencia, 46014

Spain

Sahlgrenska Universitetssjukhuset

Gothenburg, Västra Götaland County SE-41346

Sweden

Centre Hospitalier Universitaire Vaudois Lausanne

Lausanne, 1011

Switzerland

Queen Elizabeth Hospital Birmingham

Birmingham, England B15 2GW

United Kingdom

Freeman Hospital

Newcastle upon Tyne, England NE7 7DN

United Kingdom

Royal Marsden Hospital

Chelsea, London SW3 6JJ

United Kingdom

Beaston West of Scotland Canter Centre

Glasgow, G120YN

United Kingdom

Guy's Hospital

London, SE1 9RT

United Kingdom

Sarah Cannon Research Institute UK

London, W1G 6AD

United Kingdom