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

NCT ID: NCT05727904

Last Updated: 2025-07-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

670 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-30

Study Completion Date

2030-03-01

Brief Summary

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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

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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.

Conditions

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Metastatic Melanoma Unresectable Melanoma Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A

Lifileucel plus Pembrolizumab

Group Type EXPERIMENTAL

Lifileucel plus Pembrolizumab

Intervention Type 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.

Arm B

Pembrolizumab alone with Optional Crossover Period

Group Type ACTIVE_COMPARATOR

Pembrolizumab with Optional Crossover Period

Intervention Type 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.

Interventions

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Lifileucel 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.

Intervention Type BIOLOGICAL

Pembrolizumab 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.

Intervention Type BIOLOGICAL

Other Intervention Names

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LN-144 Pembrolizumab

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Iovance Biotherapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Iovance Biotherapeutics Study Team

Role: STUDY_DIRECTOR

Iovance Biotherapeutics

Locations

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University of Alabama at Birmingham: The Kirklin Clinic

Birmingham, Alabama, United States

Site Status RECRUITING

City of Hope

Duarte, California, United States

Site Status RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

California Pacific Medical Center

San Francisco, California, United States

Site Status RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status RECRUITING

Orlando Health Cancer Institute

Orlando, Florida, United States

Site Status RECRUITING

University of Illinois Hospital & Health Sciences System

Chicago, Illinois, United States

Site Status RECRUITING

University of Kansas

Kansas City, Kansas, United States

Site Status RECRUITING

University of Louisville - James Graham Brown Cancer Center

Louisville, Kentucky, United States

Site Status RECRUITING

National Cancer Institute

Bethesda, Maryland, United States

Site Status RECRUITING

Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center

Detroit, Michigan, United States

Site Status RECRUITING

Henry Ford Health

Detroit, Michigan, United States

Site Status RECRUITING

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

Lebanon, New Hampshire, United States

Site Status RECRUITING

MD Anderson Cancer Center at Cooper

Camden, New Jersey, United States

Site Status RECRUITING

Oncology Hematology Care

Cincinnati, Ohio, United States

Site Status RECRUITING

Ohio State University

Columbus, Ohio, United States

Site Status RECRUITING

St. Luke's Cancer Center - Anderson

Easton, Pennsylvania, United States

Site Status RECRUITING

Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Baptist Cancer Center

Bartlett, Tennessee, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status RECRUITING

Swedish Cancer Institute

Edmonds, Washington, United States

Site Status RECRUITING

Greenslopes Private Hospital

Greenslopes, Queensland, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Site Status RECRUITING

Flinders Medical Centre

Bedford Park, , Australia

Site Status RECRUITING

Westmead Hospital

Westmead, , Australia

Site Status RECRUITING

Universitair Ziekenhuis Brussel - Oncologisch Centrum

Jette, , Belgium

Site Status RECRUITING

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Site Status RECRUITING

Princess Margaret Cancer Centre

Toronto, , Canada

Site Status RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status RECRUITING

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

Nantes, , France

Site Status RECRUITING

Hopital Saint Louis

Paris, , France

Site Status RECRUITING

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Site Status RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, , Germany

Site Status RECRUITING

Klinikum Rechts der Isar der Technischen Universität München

Munich, , Germany

Site Status RECRUITING

Hadassah Medical Center

Jerusalem, , Israel

Site Status RECRUITING

Sheba Medical Center

Ramat Gan, , Israel

Site Status RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status RECRUITING

Istituto Romagnolo per lo Studio dei Tumori

Meldola, Forlì-Cesena, Italy

Site Status RECRUITING

Centro di Riferimento Oncologico IRCCS

Aviano, Friuli Venezia Giulia, Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, Italy

Site Status RECRUITING

Istituto Europeo Di Oncologia

Milan, , Italy

Site Status RECRUITING

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

Napoli, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Senese

Siena, , Italy

Site Status RECRUITING

Nederlands Kanker Instituut

Amsterdam, , Netherlands

Site Status RECRUITING

Bundang Medical Center - CHA University

Seongnam-si, Gyeonggi-do, South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status RECRUITING

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Site Status RECRUITING

Hospital Regional Universitario de Malaga - Hospital General

Málaga, Málaga, Spain

Site Status RECRUITING

Instituto Oncologico Rosell

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitari Vall dHebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status RECRUITING

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, , Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status RECRUITING

Hospital 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Madrid Sanchinarro - CIOCC

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Quirónsalud Madrid

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status RECRUITING

Clínica Universitaria de Navarra

Pamplona, , Spain

Site Status RECRUITING

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status RECRUITING

Consorcio Hospital General Universitario de Valencia

Valencia, , Spain

Site Status RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, Västra Götaland County, Sweden

Site Status RECRUITING

Centre Hospitalier Universitaire Vaudois Lausanne

Lausanne, , Switzerland

Site Status RECRUITING

Queen Elizabeth Hospital Birmingham

Birmingham, England, United Kingdom

Site Status RECRUITING

Freeman Hospital

Newcastle upon Tyne, England, United Kingdom

Site Status RECRUITING

Royal Marsden Hospital

Chelsea, London, United Kingdom

Site Status RECRUITING

Beaston West of Scotland Canter Centre

Glasgow, , United Kingdom

Site Status RECRUITING

Guy's Hospital

London, , United Kingdom

Site Status RECRUITING

Sarah Cannon Research Institute UK

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Belgium Canada France Germany Israel Italy Netherlands South Korea Spain Sweden Switzerland United Kingdom

Central Contacts

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Iovance Biotherapeutics https://www.tilvance-301.com

Role: CONTACT

1-844-845-4682

Iovance Biotherapeutics Study Team

Role: CONTACT

1-844-845-4682

Other Identifiers

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TILVANCE-301

Identifier Type: OTHER

Identifier Source: secondary_id

TILVANCE

Identifier Type: OTHER

Identifier Source: secondary_id

IOV-MEL-301

Identifier Type: -

Identifier Source: org_study_id

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