Metastatic MelanomaPhase 3NCT05727904
Study to Investigate Lifileucel Regimen Plus Pembrolizumab Compared With Pembrolizumab Alone in Participants With Untreated Advanced Melanoma.
A Phase 3 study testing Lifileucel plus Pembrolizumab and Pembrolizumab with Optional Crossover Period in people with Metastatic Melanoma and Unresectable Melanoma, run by Iovance Biotherapeutics, Inc. at 82 sites in 16 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Metastatic Melanoma, Unresectable Melanoma, Melanoma
- What is being tested?
- Lifileucel plus Pembrolizumab and Pembrolizumab with Optional Crossover Period
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 670 participants
- Where
- 82 sitesin 16 countries
- Study dates
- 30 Mar 2023to 1 Mar 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
- Other protocol defined inclusion/exclusion criteria could apply.
Trial locations and contacts
82 sites in 16 countries. Contact the study team or a site near you to ask about taking part.
Iovance Biotherapeutics https://www.tilvance-301.com contact
82 sites in 16 countries
United States24 sites, 16 recruiting
- Recruiting
University of Colorado Cancer Center
Aurora, Colorado, 80045
- Recruiting
Baptist Cancer Center
Bartlett, Tennessee, 37920
- Recruiting
National Cancer Institute
Bethesda, Maryland, 20814
- Recruiting
University of Alabama at Birmingham: The Kirklin Clinic
Birmingham, Alabama, 35233
- Recruiting
MD Anderson Cancer Center at Cooper
Camden, New Jersey, 08103
- Withdrawn
University of Illinois Hospital & Health Sciences System
Chicago, Illinois, 60612
- Recruiting
Oncology Hematology Care
Cincinnati, Ohio, 45226
- Recruiting
Ohio State University
Columbus, Ohio, 43201
- Withdrawn
Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
Detroit, Michigan, 48201
- Withdrawn
Henry Ford Health
Detroit, Michigan, 48202
- Recruiting
City of Hope
Duarte, California, 91010
- Withdrawn
St. Luke's Cancer Center - Anderson
Easton, Pennsylvania, 18045
- Recruiting
Swedish Cancer Institute
Edmonds, Washington, 98026
- Withdrawn
University of Kansas
Kansas City, Kansas, 66205
- Recruiting
Dartmouth-Hitchcock Medical Center (DHMC) - Norris Cotton Cancer Center
Lebanon, New Hampshire, 03756
- Recruiting
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90007
- Withdrawn
University of Louisville - James Graham Brown Cancer Center
Louisville, Kentucky, 40202
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55455
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
- Recruiting
Orlando Health Cancer Institute
Orlando, Florida, 32806
- Recruiting
Allegheny Health Network
Pittsburgh, Pennsylvania, 15224
- Withdrawn
Virginia Commonwealth University
Richmond, Virginia, 23298
- Recruiting
Intermountain Health
Salt Lake City, Utah, 84112
- Withdrawn
California Pacific Medical Center
San Francisco, California, 94107
Spain16 sites, 15 recruiting
- Recruiting
Institut Català d'Oncologia (ICO)
Barcelona, Spain, 8908
- Recruiting
Instituto Oncologico Rosell
Barcelona, 08028
- Withdrawn
Hospital Universitari Vall dHebron
Barcelona, 08035
- Recruiting
Hospital Clinic de Barcelona
Barcelona, 8036
- Recruiting
ICO l'Hospitalet - Hospital Duran i Reynals
Barcelona, 8908
- Recruiting
HM Centro Integral Oncologico Clara Campal
Madrid, Spain, 28050
- Recruiting
Hospital General Universitario Gregorio Maranon
Madrid, 28007
- Recruiting
Hospital 12 de Octubre
Madrid, 28041
- Recruiting
Hospital Universitario Madrid Sanchinarro - CIOCC
Madrid, 28050
- Recruiting
Hospital Universitario Quirónsalud Madrid
Madrid, 28223
- Recruiting
Hospital Universitario Ramon y Cajal
Madrid
- Recruiting
Hospital Regional Universitario de Malaga - Hospital General
Málaga, Málaga, 29016
- Recruiting
Clínica Universitaria de Navarra
Pamplona, 31008
- Recruiting
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008
- Recruiting
Hospital Universitario Virgen Macarena
Seville, 41009
- Recruiting
Consorcio Hospital General Universitario de Valencia
Valencia, 46014
Germany6 sites, 6 recruiting
- Recruiting
Charité - Universitätsmedizin Berlin
Berlin, Germany, 13353
- Recruiting
Universitätsklinikum Carl Gustav Carus
Dresden, 1307
- Recruiting
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20251
- Recruiting
Universitätsklinikum Schleswig-Holstein - Campus Lübeck
Lübeck, 23562
- Recruiting
Klinikum Rechts der Isar der Technischen Universität München
Munich, 81675
- Recruiting
Universitätsklinikum Würzburg
Würzburg, Germany, 97080
Italy6 sites, 5 recruiting
- Recruiting
Centro di Riferimento Oncologico IRCCS
Aviano, Friuli Venezia Giulia, 33081
- Recruiting
Istituto Romagnolo per lo Studio dei Tumori
Meldola, Forlì-Cesena, 47014
- Withdrawn
Istituto Europeo Di Oncologia
Milan, 20139
- Recruiting
Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale
Naples, Napoli, 80131
- Recruiting
Azienda Ospedaliero Universitaria Pisana
Pisa, Tuscany, 56100
- Recruiting
Azienda Ospedaliera Universitaria Senese
Siena
United Kingdom6 sites, 6 recruiting
- Recruiting
Queen Elizabeth Hospital Birmingham
Birmingham, England, B15 2GW
- Recruiting
Royal Marsden Hospital
Chelsea, London, SW3 6JJ
- Recruiting
Beaston West of Scotland Canter Centre
Glasgow, G120YN
- Recruiting
Guy's Hospital
London, SE1 9RT
- Recruiting
Sarah Cannon Research Institute UK
London, W1G 6AD
- Recruiting
Freeman Hospital
Newcastle upon Tyne, England, NE7 7DN
Australia5 sites, 5 recruiting
- Recruiting
Flinders Medical Centre
Bedford Park, 5042
- Recruiting
Greenslopes Private Hospital
Greenslopes, Queensland, 4120
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
- Recruiting
Fiona Stanley Hospital
Murdoch, Western Australia, 6150
- Recruiting
Westmead Hospital
Westmead, NSW 2145
South Korea5 sites, 5 recruiting
- Recruiting
Bundang Medical Center - CHA University
Seongnam-si, Gyeonggi-do
- Recruiting
Samsung Medical Center
Seoul, South Korea, 135-890
- Recruiting
Korea University Anam Hospital
Seoul, 2841
- Recruiting
Seoul National University Hospital
Seoul, 3080
- Recruiting
Severance Hospital, Yonsei University Health System
Seoul, 3722
France3 sites, 3 recruiting
- Recruiting
Institut Paoli Calmettes
Marseille, 13009
- Recruiting
Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu
Nantes, 44093
- Recruiting
Hopital Saint Louis
Paris, 75475
Israel3 sites, 2 recruiting
- Recruiting
Hadassah Medical Center
Jerusalem
- Recruiting
Sheba Medical Center
Ramat Gan, 52621
- Withdrawn
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906
Canada2 sites, 2 recruiting
- Recruiting
Centre hospitalier de l'Université de Montréal
Montreal, Quebec, H2L 4M1
- Recruiting
Princess Margaret Cancer Centre
Toronto, M5G
Belgium1 site, 1 recruiting
- Recruiting
Universitair Ziekenhuis Brussel - Oncologisch Centrum
Jette
Finland1 site, 1 recruiting
- Recruiting
Helsinki University Hospital Comprehensive Cancer Center
Helsinki, Finland, 290
Netherlands1 site, 1 recruiting
- Recruiting
Nederlands Kanker Instituut
Amsterdam, 1066 CX
Singapore1 site, 1 recruiting
- Recruiting
National Cancer Centre Singapore
Singapore, Singapore, 168582
Sweden1 site, 1 recruiting
- Recruiting
Sahlgrenska Universitetssjukhuset
Gothenburg, Västra Götaland County, SE-41346
Switzerland1 site, 1 recruiting
- Recruiting
Centre Hospitalier Universitaire Vaudois Lausanne
Lausanne, 1011
About this study
Official title: 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.
Read the 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.
- Conditions
- Metastatic Melanoma, Unresectable Melanoma, Melanoma
- Being tested
- Lifileucel plus Pembrolizumab, Pembrolizumab with Optional Crossover Period
- 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
- Medical subject headings
- Melanoma, Skin Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lifileucel plus PembrolizumabBiological
Also called LN-144, 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.
Pembrolizumab with Optional Crossover PeriodBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Lifileucel plus Pembrolizumab Receives: Biological: Lifileucel plus Pembrolizumab |
| Arm B | Active comparator | Pembrolizumab alone with Optional Crossover Period Receives: Biological: Pembrolizumab with Optional Crossover Period |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 years total duration
Secondary outcomes (4)
Overall Survival
To compare the efficacy of lifileucel plus pembrolizumab with the efficacy of pembrolizumab alone measured by overall survival (OS)
Measured: 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
Measured: 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
Measured: 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
Measured: 5 years total duration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2023
- Study start30 Mar 2023
- Primary completion1 Mar 2028 (estimated)
- Study completion1 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 670 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Iovance Biotherapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Iovance Biotherapeutics Study Team, Study director, Iovance Biotherapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05727904
- Sponsor's protocol ID
- IOV-MEL-301
- Other IDs
- TILVANCE-301, TILVANCE
- Status last verified
- Sep 2026
- First submitted
- 6 Feb 2023
- Last updated
- 24 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available