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

NCT05727904 · tracked via the Priya Life Science USA tracker

Sponsor

Iovance Biotherapeutics, Inc.

Phase

Phase 3

Started

2023-03-30

Last updated

2026-06-26

Condition(s) studied

Metastatic MelanomaUnresectable MelanomaMelanoma

Investigational drug(s) / intervention(s)

Lifileucel plus PembrolizumabPembrolizumab with Optional Crossover Period

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.

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.

Study 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

Sex

ALL

Min age

18 Years

Max age

70 Years

Healthy volunteers

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.

Primary outcome measure(s)

Objective Response Rate and Progression Free Survival — 5 years total duration
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

Trial sites (81)

Facility	City	Region	Status
University of Alabama at Birmingham: The Kirklin Clinic	Birmingham	Alabama	Recruiting
City of Hope	Duarte	California	Recruiting
USC Norris Comprehensive Cancer Center	Los Angeles	California	Recruiting
California Pacific Medical Center	San Francisco	California	Recruiting
University of Colorado Cancer Center	Aurora	Colorado	Recruiting
Orlando Health Cancer Institute	Orlando	Florida	Recruiting
University of Illinois Hospital & Health Sciences System	Chicago	Illinois	Withdrawn
University of Kansas	Kansas City	Kansas	Withdrawn
University of Louisville - James Graham Brown Cancer Center	Louisville	Kentucky	Withdrawn
National Cancer Institute	Bethesda	Maryland	Recruiting
Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center	Detroit	Michigan	Withdrawn
Henry Ford Health	Detroit	Michigan	Recruiting
University of Minnesota	Minneapolis	Minnesota	Recruiting
Dartmouth-Hitchcock Medical Center (DHMC) - Norris Cotton Cancer Center	Lebanon	New Hampshire	Recruiting
MD Anderson Cancer Center at Cooper	Camden	New Jersey	Recruiting
Oncology Hematology Care	Cincinnati	Ohio	Recruiting
Ohio State University	Columbus	Ohio	Recruiting
St. Luke's Cancer Center - Anderson	Easton	Pennsylvania	Withdrawn
Allegheny Health Network	Pittsburgh	Pennsylvania	Recruiting
Baptist Cancer Center	Bartlett	Tennessee	Recruiting
SCRI Oncology Partners	Nashville	Tennessee	Recruiting
Intermountain Health	Salt Lake City	Utah	Recruiting
Virginia Commonwealth University	Richmond	Virginia	Withdrawn
Swedish Cancer Institute	Edmonds	Washington	Recruiting
Greenslopes Private Hospital	Greenslopes	Queensland	Recruiting
Peter MacCallum Cancer Centre	Melbourne	Victoria	Recruiting
Fiona Stanley Hospital	Murdoch	Western Australia	Recruiting
Flinders Medical Centre	Bedford Park	Australia	Recruiting
Westmead Hospital	Westmead	Australia	Recruiting
Universitair Ziekenhuis Brussel - Oncologisch Centrum	Jette	Belgium	Recruiting
Centre hospitalier de l'Université de Montréal	Montreal	Quebec	Recruiting
Princess Margaret Cancer Centre	Toronto	Canada	Recruiting
Helsinki University Hospital Comprehensive Cancer Center	Helsinki	Finland	Recruiting
Institut Paoli Calmettes	Marseille	France	Recruiting
Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu	Nantes	France	Recruiting
Hopital Saint Louis	Paris	France	Recruiting
Charité - Universitätsmedizin Berlin	Berlin	Germany	Recruiting
Universitätsklinikum Carl Gustav Carus	Dresden	Germany	Recruiting
Universitätsklinikum Hamburg-Eppendorf	Hamburg	Germany	Recruiting
Universitätsklinikum Schleswig-Holstein - Campus Lübeck	Lübeck	Germany	Recruiting

+ 41 more sites — see the full list on the official registry below.

More Iovance Biotherapeutics, Inc. trials in the USA

A Study to Investigate the Safety and Efficacy of IOV-3001 in Adults With Advanced Melanoma Who Will Receive Lifileucel Recruiting

A Study of IOV-5001 in Adults With Advanced Solid Tumors Starting soon

A Study of Lifileucel (Tumor-infiltrating Lymphocytes) in Adults With Advanced Melanoma Active, not recruiting

Study of Autologous Tumor-Infiltrating Lymphocytes in Pediatric, Adolescent, and Young Adult Participants Active, not recruiting

Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer Recruiting

Other trials for the same condition

A Phase 1/2 Study of BA3071 in Patients With Solid Tumors Active, not recruiting

ENB003 Plus Pembrolizumab Phase 1b/2a in Solid Tumors Active, not recruiting

A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an Advanced Solid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051) Recruiting

A Study to Evaluate ABP 206 Compared With OPDIVO® (Nivolumab) in Subjects With Unresectable or Metastatic Melanoma Active, not recruiting

Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC Active, not recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05727904 on ClinicalTrials.gov ↗ ← All trials in the USA