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

NCT05727904 | Recruiting Phase 3 FDA Drug

• 3 other identifiers: IOV-MEL-301TILVANCE-301TILVANCE
• Study Type: interventional
• Target: 670
• Locations: 14 countries
• Sites: 72

Brief 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.

Conditions

Metastatic Melanoma; Unresectable Melanoma; Melanoma

Keywords

Tumor Infiltrating Lymphocytes; TIL; Metastatic Melanoma; Unresectable Melanoma; Cell Therapy; Cellular Immuno-therapy; IL-2; Non-myeloablative lymphodepletion (NMALD); Check point inhibitor; Melanoma; Lifileucel; Stage III Melanoma; Stage IV Melanoma; Skin cancer; Skin cancer types; Malignant melanoma; Autologous Adoptive Cell Therapy; Autologous Adoptive Cell Transfer; LN-144; Pembrolizumab; Pembro; Adjuvant/Neo-adjuvant; BRAF/MEK; ICI; BRAF v600; Immune checkpoint inhibitor; Tumor infiltrating T-cells; TILVANCE; TILVANCE-301

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Overall Survival

  7 years total duration

• Complete Response Rate, Duration of Response and Event Free Survival

  5 years total duration

• Objective Response Rate, Progression Free Survival, Complete Response Rate, Duration of Responses, Event Free Survival and PFS2

  5 years total duration

• Adverse Events

  5 years total duration

Study Arms (2)

Arm A

EXPERIMENTAL

Lifileucel plus Pembrolizumab

Biological: Lifileucel plus Pembrolizumab

Arm B

ACTIVE COMPARATOR

Pembrolizumab alone with Optional Crossover Period

Biological: Pembrolizumab with 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.

Also known as: LN-144, Pembrolizumab

Arm A

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.

Arm B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Iovance Biotherapeutics, Inc.: lead

Study Sites (72)

University of Alabama at Birmingham: The Kirklin Clinic

Birmingham, Alabama, 35233, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90007, United States

RECRUITING

California Pacific Medical Center

San Francisco, California, 94107, United States

RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

RECRUITING

University of Illinois Hospital & Health Sciences System

Chicago, Illinois, 60612, United States

RECRUITING

University of Kansas

Kansas City, Kansas, 66205, United States

RECRUITING

University of Louisville - James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

RECRUITING

National Cancer Institute

Bethesda, Maryland, 20814, United States

RECRUITING

Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center

Detroit, Michigan, 48201, United States

RECRUITING

Henry Ford Health

Detroit, Michigan, 48202, United States

RECRUITING

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

Lebanon, New Hampshire, 03756, United States

RECRUITING

MD Anderson Cancer Center at Cooper

Camden, New Jersey, 08103, United States

RECRUITING

Oncology Hematology Care

Cincinnati, Ohio, 45226, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43201, United States

RECRUITING

St. Luke's Cancer Center - Anderson

Easton, Pennsylvania, 18045, United States

RECRUITING

Allegheny Health Network

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Baptist Cancer Center

Bartlett, Tennessee, 37920, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

Swedish Cancer Institute

Edmonds, Washington, 98026, United States

RECRUITING

Greenslopes Private Hospital

Greenslopes, Queensland, 4120, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

RECRUITING

Flinders Medical Centre

Bedford Park, 5042, Australia

RECRUITING

Westmead Hospital

Westmead, NSW 2145, Australia

RECRUITING

Universitair Ziekenhuis Brussel - Oncologisch Centrum

Jette, Belgium

RECRUITING

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, H2L 4M1, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, M5G, Canada

RECRUITING

Institut Paoli Calmettes

Marseille, 13009, France

RECRUITING

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

Nantes, 44093, France

RECRUITING

Hopital Saint Louis

Paris, 75475, France

RECRUITING

Universitätsklinikum Carl Gustav Carus

Dresden, 1307, Germany

RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20251, Germany

RECRUITING

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, 23562, Germany

RECRUITING

Klinikum Rechts der Isar der Technischen Universität München

Munich, 81675, Germany

RECRUITING

Hadassah Medical Center

Jerusalem, Israel

RECRUITING

Sheba Medical Center

Ramat Gan, 52621, Israel

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

RECRUITING

Istituto Romagnolo per lo Studio dei Tumori

Meldola, Forlì-Cesena, 47014, Italy

RECRUITING

Centro di Riferimento Oncologico IRCCS

Aviano, Friuli Venezia Giulia, 33081, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, 56100, Italy

RECRUITING

Istituto Europeo Di Oncologia

Milan, 20139, Italy

RECRUITING

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

Napoli, 80131, Italy

RECRUITING

Azienda Ospedaliera Universitaria Senese

Siena, Italy

RECRUITING

Nederlands Kanker Instituut

Amsterdam, 1066 CX, Netherlands

RECRUITING

Bundang Medical Center - CHA University

Seongnam-si, Gyeonggi-do, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 3080, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 3722, South Korea

RECRUITING

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

RECRUITING

Hospital Regional Universitario de Malaga - Hospital General

Málaga, Málaga, 29016, Spain

RECRUITING

Instituto Oncologico Rosell

Barcelona, 08028, Spain

RECRUITING

Hospital Universitari Vall dHebron

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

RECRUITING

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, 8908, Spain

RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

RECRUITING

Hospital 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario Madrid Sanchinarro - CIOCC

Madrid, 28050, Spain

RECRUITING

Hospital Universitario Quirónsalud Madrid

Madrid, 28223, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, Spain

RECRUITING

Clínica Universitaria de Navarra

Pamplona, 31008, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

RECRUITING

Consorcio Hospital General Universitario de Valencia

Valencia, 46014, Spain

RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, Västra Götaland County, SE-41346, Sweden

RECRUITING

Centre Hospitalier Universitaire Vaudois Lausanne

Lausanne, 1011, Switzerland

RECRUITING

Queen Elizabeth Hospital Birmingham

Birmingham, England, B15 2GW, United Kingdom

RECRUITING

Freeman Hospital

Newcastle upon Tyne, England, NE7 7DN, United Kingdom

RECRUITING

Royal Marsden Hospital

Chelsea, London, SW3 6JJ, United Kingdom

RECRUITING

Beaston West of Scotland Canter Centre

Glasgow, G120YN, United Kingdom

RECRUITING

Guy's Hospital

London, SE1 9RT, United Kingdom

RECRUITING

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

lifileucel; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Iovance Biotherapeutics Study Team

  Iovance Biotherapeutics

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

1-844-845-4682; Clinical.Inquiries@iovance.com

Iovance Biotherapeutics Study Team

CONTACT

1-844-845-4682; Clinical.Inquiries@iovance.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: February 6, 2023
• First Posted: February 14, 2023
• Study Start: March 30, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: July 8, 2025

Record last verified: 2025-07

Locations

SE (1); FR (3); NL (1); CH (1); IL (3); KR (3); IT (6); US (22); CA (2); ES (14); GB (6); AU (5); DE (4); BE (1)