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

April 29, 2024 updated by: Iovance Biotherapeutics, Inc.

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

Intervention / Treatment

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

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • 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
  • Canada
    • Quebec
      • Montréal, Quebec, Canada, H2L 4M1
        • Recruiting
        • Centre Hospitalier de l'Universite de Montreal
  • France
      • Nantes, France, 44093
        • Recruiting
        • Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Recruiting
        • Nederlands Kanker Instituut
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall dHebron
      • Barcelona, Spain, 08028
        • Recruiting
        • Instituto Oncologico Rosell
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital 12 de Octubre
      • Madrid, Spain, 28223
        • Recruiting
        • Hospital Universitario QuironSalud Madrid
      • Madrid, Spain, 28050
        • Recruiting
        • Hospital Universitario Madrid Sanchinarro - CIOCC
      • Sevilla, 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 Marques de Valdecilla
    • Málaga
      • Malaga, Málaga, Spain, 29016
        • Recruiting
        • Hospital Regional Universitario de Malaga - Hospital General
  • Sweden
    • Vastra Gotalands Lan
      • Göteborg, Vastra Gotalands Lan, Sweden, SE-41346
        • Recruiting
        • Sahlgrenska Universitetssjukhuset
  • 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
    • Florida
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Orlando Health Cancer Institute
    • Kansas
      • Kansas City, Kansas, United States, 66205
        • Recruiting
        • University of Kansas
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • University of Louisville - James Graham Brown Cancer Center
    • Maryland
      • Bethesda, Maryland, United States, 20814
        • Recruiting
        • National Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Recruiting
        • MD Anderson Cancer Center at Cooper
    • Pennsylvania
      • Easton, Pennsylvania, United States, 18045
        • Recruiting
        • 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
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: 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
5 years total duration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 7 years total duration
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
Time Frame: 5 years total duration
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
Time Frame: 5 years total duration
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
Time Frame: 5 years total duration
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

This is where you will find people and organizations involved with this study.

Sponsor

Iovance Biotherapeutics, Inc.

Investigators

  • Study Director: Iovance Biotherapeutics Study Team, Iovance Biotherapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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 30, 2024

Last Update Submitted That Met QC Criteria

April 29, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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