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

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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Metastatic Melanoma; Unresectable Melanoma
• Intervention / Treatment: Biological: Lifileucel plus Pembrolizumab; Biological: Pembrolizumab with 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.

• Study Type: Interventional
• Enrollment (Estimated): 670
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Iovance Biotherapeutics Study Team; Phone Number: 1-844-845-4682; Email: Clinical.Inquiries@iovance.com
• Study Contact Backup: Name: Iovance Biotherapeutics https://www.tilvance-301.com; Phone Number: 1-844-845-4682; Email: Clinical.Inquiries@iovance.com

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Recruiting
    • Flinders Medical Centre
  • Westmead, Australia, NSW 2145
    • Recruiting
    • Westmead Hospital
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Recruiting
      • Greenslopes Private Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Recruiting
      • Fiona Stanley Hospital
• Belgium
  • Jette, Belgium
    • Recruiting
    • Universitair Ziekenhuis Brussel - Oncologisch Centrum
• Canada
  • Toronto, Canada, M5G
    • Recruiting
    • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Recruiting
      • Centre Hospitalier de L'Universite de Montreal
• France
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
  • Nantes, France, 44093
    • Recruiting
    • Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu
  • Paris, France, 75475
    • Recruiting
    • Hopital Saint Louis
• Germany
  • Dresden, Germany, 1307
    • Recruiting
    • Universitätsklinikum Carl Gustav Carus
  • Hamburg, Germany, 20251
    • Recruiting
    • Universitätsklinikum Hamburg-Eppendorf
  • Lübeck, Germany, 23562
    • Recruiting
    • Universitatsklinikum Schleswig-Holstein - Campus Lubeck
  • Munich, Germany, 81675
    • Recruiting
    • Klinikum rechts der Isar der Technischen Universität München
  • Germany
    • Berlin, Germany, Germany, 13353
      • Recruiting
      • Charité - Universitätsmedizin Berlin
• Israel
  • Jerusalem, Israel
    • Recruiting
    • Hadassah Medical Center
  • Ramat Gan, Israel, 52621
    • Recruiting
    • Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel Aviv Sourasky Medical Center
• Italy
  • Milan, Italy, 20139
    • Withdrawn
    • Istituto Europeo di Oncologia
  • Siena, Italy
    • Recruiting
    • Azienda Ospedaliera Universitaria Senese
  • Forlì-Cesena
    • Meldola, Forlì-Cesena, Italy, 47014
      • Recruiting
      • Istituto Romagnolo Per Lo Studio Dei Tumori
  • Friuli Venezia Giulia
    • Aviano, Friuli Venezia Giulia, Italy, 33081
      • Recruiting
      • Centro di Riferimento Oncologico IRCCS
  • Napoli
    • Naples, Napoli, Italy, 80131
      • Recruiting
      • Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale
  • Tuscany
    • Pisa, Tuscany, Italy, 56100
      • Recruiting
      • Azienda Ospedaliero Universitaria Pisana
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Recruiting
    • Nederlands Kanker Instituut
• South Korea
  • Seoul, South Korea, 3722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 3080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 2841
    • Recruiting
    • Korea University Anam Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea
      • Recruiting
      • Bundang Medical Center - CHA University
  • South Korea
    • Seoul, South Korea, South Korea, 135-890
      • Recruiting
      • Samsung Medical Center
• Spain
  • Barcelona, Spain, 8036
    • Recruiting
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08028
    • Recruiting
    • Instituto Oncologico Rosell
  • Barcelona, Spain, 8908
    • Recruiting
    • ICO l'Hospitalet - Hospital Duran i Reynals
  • Barcelona, Spain, 08035
    • Withdrawn
    • Hospital Universitari Vall dHebron
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital 12 de Octubre
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28223
    • Recruiting
    • Hospital Universitario Quironsalud Madrid
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario Madrid Sanchinarro - CIOCC
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Universitaria de Navarra
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46014
    • Recruiting
    • Consorcio Hospital General Universitario de Valencia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Recruiting
      • Hospital Universitario Marqués de Valdecilla
  • Málaga
    • Málaga, Málaga, Spain, 29016
      • Recruiting
      • Hospital Regional Universitario de Malaga - Hospital General
• Sweden
  • Västra Götaland County
    • Gothenburg, Västra Götaland County, Sweden, SE-41346
      • Recruiting
      • Sahlgrenska Universitetssjukhuset
• Switzerland
  • Lausanne, Switzerland, 1011
    • Recruiting
    • Centre Hospitalier Universitaire Vaudois Lausanne
• United Kingdom
  • Glasgow, United Kingdom, G120YN
    • Recruiting
    • Beaston West of Scotland Canter Centre
  • London, United Kingdom, W1G 6AD
    • Recruiting
    • Sarah Cannon Research Institute UK
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's Hospital
  • England
    • Birmingham, England, United Kingdom, B15 2GW
      • Recruiting
      • Queen Elizabeth Hospital Birmingham
    • Newcastle upon Tyne, England, United Kingdom, NE7 7DN
      • Recruiting
      • Freeman Hospital
  • London
    • Chelsea, London, United Kingdom, SW3 6JJ
      • Recruiting
      • Royal Marsden Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham: The Kirklin Clinic
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
    • Los Angeles, California, United States, 90007
      • Recruiting
      • USC Norris Comprehensive Cancer Center
    • San Francisco, California, United States, 94107
      • Recruiting
      • California Pacific Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Cancer Center
  • Florida
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Orlando Health Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Withdrawn
      • University of Illinois Hospital & Health Sciences System
  • Kansas
    • Kansas City, Kansas, United States, 66205
      • Withdrawn
      • University of Kansas
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Withdrawn
      • University of Louisville - James Graham Brown Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Recruiting
      • National Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health
    • Detroit, Michigan, United States, 48201
      • Withdrawn
      • Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Recruiting
      • Dartmouth-Hitchcock Medical Center (DHMC) - Norris Cotton Cancer Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Recruiting
      • MD Anderson Cancer Center at Cooper
  • Ohio
    • Cincinnati, Ohio, United States, 45226
      • Recruiting
      • Oncology Hematology Care
    • Columbus, Ohio, United States, 43201
      • Recruiting
      • Ohio State University
  • Pennsylvania
    • Easton, Pennsylvania, United States, 18045
      • Withdrawn
      • St. Luke's Cancer Center - Anderson
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • Allegheny Health Network
  • Tennessee
    • Bartlett, Tennessee, United States, 37920
      • Recruiting
      • Baptist Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Withdrawn
      • Virginia Commonwealth University
  • Washington
    • Edmonds, Washington, United States, 98026
      • Recruiting
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Lifileucel plus Pembrolizumab	Biological: 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.; Other Names: Pembrolizumab; LN-144
Active Comparator: Arm B; Pembrolizumab alone with Optional Crossover Period	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate and Progression Free Survival	To compare the efficacy of lifileucel plus pembrolizumab with the efficacy of pembrolizumab alone measured by objective response rate (ORR) and progression-free survival (PFS) assessed by the blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	5 years total duration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	To compare the efficacy of lifileucel plus pembrolizumab with the efficacy of pembrolizumab alone measured by overall survival (OS)	7 years total duration
Complete Response Rate, Duration of Response and Event Free Survival	To compare the efficacy of lifileucel plus pembrolizumab with the efficacy of pembrolizumab alone measured by complete response (CR) rate and duration of response (DOR) and event- free survival (EFS) assessed by the BIRC per RECIST v1.1	5 years total duration
Objective Response Rate, Progression Free Survival, Complete Response Rate, Duration of Responses, Event Free Survival and PFS2	To compare the efficacy of lifileucel plus pembrolizumab with the efficacy of pembrolizumab alone measured by ORR, PFS, CR rate, DOR, and EFS assessed by the investigator per RECIST v1.1 and PFS2 assessed by the investigator	5 years total duration
Adverse Events	To characterize the safety and tolerability profile of lifileucel plus pembrolizumab and pembrolizumab alone in participants with unresectable or metastatic melanoma	5 years total duration

Collaborators and Investigators

• Sponsor: Iovance Biotherapeutics, Inc.
• Investigators: Study Director: Iovance Biotherapeutics Study Team, Iovance Biotherapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (Actual): February 14, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Pembrolizumab; Melanoma; Malignant melanoma; Skin cancer; Tumor Infiltrating Lymphocytes; IL-2; TIL; Immune checkpoint inhibitor; Autologous Adoptive Cell Transfer; Autologous Adoptive Cell Therapy; Cellular Immuno-therapy; LN-144; Lifileucel; Metastatic Melanoma; Unresectable Melanoma; Stage IV Melanoma; ICI; Stage III Melanoma; Check point inhibitor; Skin cancer types; Non-myeloablative lymphodepletion (NMALD); Pembro; Adjuvant/Neo-adjuvant; BRAF/MEK; BRAF v600; Tumor infiltrating T-cells; TILVANCE; TILVANCE-301
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin and Connective Tissue Diseases; Melanoma; Skin Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab; lifileucel
• Other Study ID Numbers: IOV-MEL-301; TILVANCE-301 (Other Identifier: Iovance Biotherapeutics, Inc.); TILVANCE (Other Identifier: Iovance Biotherapeutics, Inc.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No