RECRUITING Phase 3 ClinicalTrials.gov

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

Sponsor: Iovance Biotherapeutics, Inc. • ClinicalTrials.gov ID: NCT05727904

Registry updated: 2026-09-24

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Description

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.

Interventions

Lifileucel plus Pembrolizumab (Biological)
A tumor sample is resected from each patient for Lifileucel manufacturing. Patients then receive Pembrolizumab followed by the lifileucel regimen which consists of non-myeloablative lymphodepletion, lifileucel infusion followed by IL-2. Patients will then continue to receive Pembrolizumab every 6 weeks until disease progression.
Pembrolizumab with Optional Crossover Period (Biological)
Patient will receive Pembrolizumab monotherapy every 6 weeks until disease progression. Upon verified confirmed disease progression by the blinded independent review central committee, patients may proceed to lifileucel monotherapy during an optional crossover period if they meet eligibility criteria. Optional crossover: A tumor sample is resected from each patient for Lifileucel manufacturing. Patients then receive the lifileucel regimen which consists of non-myeloablative lymphodepletion, lifileucel infusion followed by IL-2.

Eligibility criteria

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.

Conditions

Metastatic Melanoma Unresectable Melanoma Melanoma

Locations

University of Alabama at Birmingham: The Kirklin Clinic — Birmingham, Alabama, United States
City of Hope — Duarte, California, United States
USC Norris Comprehensive Cancer Center — Los Angeles, California, United States
California Pacific Medical Center — San Francisco, California, United States
University of Colorado Cancer Center — Aurora, Colorado, United States
Orlando Health Cancer Institute — Orlando, Florida, United States
University of Illinois Hospital & Health Sciences System — Chicago, Illinois, United States
University of Kansas — Kansas City, Kansas, United States
University of Louisville - James Graham Brown Cancer Center — Louisville, Kentucky, United States
National Cancer Institute — Bethesda, Maryland, United States
Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center — Detroit, Michigan, United States
Henry Ford Health — Detroit, Michigan, United States
University of Minnesota — Minneapolis, Minnesota, United States
Dartmouth-Hitchcock Medical Center (DHMC) - Norris Cotton Cancer Center — Lebanon, New Hampshire, United States
MD Anderson Cancer Center at Cooper — Camden, New Jersey, United States
Oncology Hematology Care — Cincinnati, Ohio, United States
Ohio State University — Columbus, Ohio, United States
St. Luke's Cancer Center - Anderson — Easton, Pennsylvania, United States
Allegheny Health Network — Pittsburgh, Pennsylvania, United States
Baptist Cancer Center — Bartlett, Tennessee, United States
SCRI Oncology Partners — Nashville, Tennessee, United States
Intermountain Health — Salt Lake City, Utah, United States
Virginia Commonwealth University — Richmond, Virginia, United States
Swedish Cancer Institute — Edmonds, Washington, United States
Greenslopes Private Hospital — Greenslopes, Queensland, Australia
Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia
Fiona Stanley Hospital — Murdoch, Western Australia, Australia
Flinders Medical Centre — Bedford Park, Australia
Westmead Hospital — Westmead, Australia
Universitair Ziekenhuis Brussel - Oncologisch Centrum — Jette, Belgium
Centre hospitalier de l'Université de Montréal — Montreal, Quebec, Canada
Princess Margaret Cancer Centre — Toronto, Canada
Helsinki University Hospital Comprehensive Cancer Center — Helsinki, Finland, Finland
Institut Paoli Calmettes — Marseille, France
Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu — Nantes, France
Hopital Saint Louis — Paris, France
Charité - Universitätsmedizin Berlin — Berlin, Germany, Germany
Universitätsklinikum Würzburg — Würzburg, Germany, Germany
Universitätsklinikum Carl Gustav Carus — Dresden, Germany
Universitätsklinikum Hamburg-Eppendorf — Hamburg, Germany
Universitätsklinikum Schleswig-Holstein - Campus Lübeck — Lübeck, Germany
Klinikum Rechts der Isar der Technischen Universität München — Munich, Germany
Hadassah Medical Center — Jerusalem, Israel
Sheba Medical Center — Ramat Gan, Israel
Tel Aviv Sourasky Medical Center — Tel Aviv, Israel
Istituto Romagnolo per lo Studio dei Tumori — Meldola, Forlì-Cesena, Italy
Centro di Riferimento Oncologico IRCCS — Aviano, Friuli Venezia Giulia, Italy
Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale — Naples, Napoli, Italy
Azienda Ospedaliero Universitaria Pisana — Pisa, Tuscany, Italy
Istituto Europeo Di Oncologia — Milan, Italy
Azienda Ospedaliera Universitaria Senese — Siena, Italy
Nederlands Kanker Instituut — Amsterdam, Netherlands
National Cancer Centre Singapore — Singapore, Singapore, Singapore
Bundang Medical Center - CHA University — Seongnam-si, Gyeonggi-do, South Korea
Samsung Medical Center — Seoul, South Korea, South Korea
Korea University Anam Hospital — Seoul, South Korea
Seoul National University Hospital — Seoul, South Korea
Severance Hospital, Yonsei University Health System — Seoul, South Korea
Hospital Universitario Marques de Valdecilla — Santander, Cantabria, Spain
Hospital Regional Universitario de Malaga - Hospital General — Málaga, Málaga, Spain
Institut Català d'Oncologia (ICO) — Barcelona, Spain, Spain
HM Centro Integral Oncologico Clara Campal — Madrid, Spain, Spain
Instituto Oncologico Rosell — Barcelona, Spain
Hospital Universitari Vall dHebron — Barcelona, Spain
Hospital Clinic de Barcelona — Barcelona, Spain
ICO l'Hospitalet - Hospital Duran i Reynals — Barcelona, Spain
Hospital General Universitario Gregorio Maranon — Madrid, Spain
Hospital 12 de Octubre — Madrid, Spain
Hospital Universitario Madrid Sanchinarro - CIOCC — Madrid, Spain
Hospital Universitario Quirónsalud Madrid — Madrid, Spain
Hospital Universitario Ramon y Cajal — Madrid, Spain
Clínica Universitaria de Navarra — Pamplona, Spain
Hospital Universitario Virgen Macarena — Seville, Spain
Consorcio Hospital General Universitario de Valencia — Valencia, Spain
Sahlgrenska Universitetssjukhuset — Gothenburg, Västra Götaland County, Sweden
Centre Hospitalier Universitaire Vaudois Lausanne — Lausanne, Switzerland
Queen Elizabeth Hospital Birmingham — Birmingham, England, United Kingdom
Freeman Hospital — Newcastle upon Tyne, England, United Kingdom
Royal Marsden Hospital — Chelsea, London, United Kingdom
Beaston West of Scotland Canter Centre — Glasgow, United Kingdom
Guy's Hospital — London, United Kingdom
Sarah Cannon Research Institute UK — London, United Kingdom

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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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