Clinical trial NCT05727904: Study to Investigate Lifileucel Regimen Plus Pembrolizumab Compared With Pembrolizumab Alone in Participants With Untreated Advanced Melanoma.
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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
Lead sponsor: Iovance Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-14
Enrollment: 670
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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 outcomes:
measure: Objective Response Rate and Progression Free Survival
timeFrame: 5 years total duration
Secondary outcomes:
measure: Overall Survival
timeFrame: 7 years total duration
measure: Complete Response Rate, Duration of Response and Event Free Survival
timeFrame: 5 years total duration
measure: Objective Response Rate, Progression Free Survival, Complete Response Rate, Duration of Responses, Event Free Survival and PFS2
timeFrame: 5 years total duration
measure: Adverse Events
timeFrame: 5 years total duration
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham: The Kirklin Clinic
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Chicago
country: United States
facility: University of Illinois Hospital & Health Sciences System
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Louisville
country: United States
facility: University of Louisville - James Graham Brown Cancer Center
state: Kentucky
city: Bethesda
country: United States
facility: National Cancer Institute
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center (DHMC) - Norris Cotton Cancer Center
state: New Hampshire
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper
state: New Jersey
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Easton
country: United States
facility: St. Luke's Cancer Center - Anderson
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Bartlett
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Edmonds
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Greenslopes
country: Australia
facility: Greenslopes Private Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Westmead
country: Australia
facility: Westmead Hospital
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel - Oncologisch Centrum
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu
city: Paris
country: France
facility: Hopital Saint Louis
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Campus Lübeck
city: Munich
country: Germany
facility: Klinikum Rechts der Isar der Technischen Universität München
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori
state: Forlì-Cesena
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico IRCCS
state: Friuli-Venezia Giulia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Milan
country: Italy
facility: Istituto Europeo Di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
city: Seongnam-si
country: Korea, Republic of
facility: Bundang Medical Center - CHA University
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Hospital General
state: Málaga
city: Barcelona
country: Spain
facility: Instituto Oncologico Rosell
city: Barcelona
country: Spain
facility: Hospital Universitari Vall dHebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro - CIOCC
city: Madrid
country: Spain
facility: Hospital Universitario Quirónsalud Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Consorcio Hospital General Universitario de Valencia
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
state: Vastra Gotalands Lan
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois Lausanne
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
state: England
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: England
city: Chelsea
country: United Kingdom
facility: Royal Marsden Hospital
state: London
city: Glasgow
country: United Kingdom
facility: Beaston West of Scotland Canter Centre
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
Study officials:
affiliation: Iovance Biotherapeutics
name: Iovance Biotherapeutics Study Team
role: STUDY_DIRECTOR
References: