RecruitingPhase 3NCT05727904

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

A Phase 3, Multicenter, Randomized, Open-label, Parallel Group, Treatment Study to Assess the Efficacy and Safety of the Lifileucel (LN-144, Autologous Tumor Infiltrating Lymphocytes [TIL]) Regimen in Combination With Pembrolizumab Compared With Pembrolizumab Monotherapy in Participants With Untreated, Unresectable or Metastatic Melanoma


Sponsor

Iovance Biotherapeutics, Inc.

Enrollment

670 participants

Start Date

Mar 30, 2023

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria7

  • Participant has a histologically or pathologically confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma.
  • 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.
  • Participant is assessed as having at least one resectable lesion (or aggregate lesions) for lifileucel generation.
  • Participant must have at least one measurable disease as defined by RECIST 1.1 following tumor resection.
  • Participants must have adequate organ function.
  • Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control.
  • Participants who are \> 70 years of age may be allowed to enroll after the investigator discusses with the medical monitor.

Exclusion Criteria9

  • Participant has melanoma of uveal/ocular origin.
  • Participant has symptomatic untreated brain metastases.
  • Participant received more than 1 prior line of therapy.
  • Participant received prior therapy for metastatic disease
  • Participants with a BRAF V600 mutation-positive tumor received prior adjuvant/neoadjuvant ICI therapy only
  • 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.
  • Participant has any form of primary or acquired immunodeficiency (eg, SCID or AIDS).
  • 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.)
  • Participant has a history of allogeneic cell or organ transplant.

Interventions

BIOLOGICALLifileucel plus Pembrolizumab

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.

BIOLOGICALPembrolizumab with Optional Crossover Period

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.


Locations(72)

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

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

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

Institut Paoli Calmettes

Marseille, France

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

Nantes, France

Hopital Saint Louis

Paris, France

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

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, Italy

Istituto Europeo Di Oncologia

Milan, Italy

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

Napoli, Italy

Azienda Ospedaliera Universitaria Senese

Siena, Italy

Nederlands Kanker Instituut

Amsterdam, Netherlands

Bundang Medical Center - CHA University

Seongnam-si, Gyeonggi-do, 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

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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NCT05727904


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