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

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ClinicalTrials.gov Identifier: NCT05727904
Recruitment Status : Recruiting
First Posted : February 14, 2023
Last Update Posted : May 16, 2024
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE February 6, 2023
First Posted Date  ICMJE February 14, 2023
Last Update Posted Date May 16, 2024
Actual Study Start Date  ICMJE March 30, 2023
Estimated Primary Completion Date March 1, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 6, 2023)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2023)
  • 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)
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Investigate Lifileucel Regimen Plus Pembrolizumab Compared With Pembrolizumab Alone in Participants With Untreated Advanced Melanoma.
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Melanoma
  • Unresectable Melanoma
  • Melanoma
Intervention  ICMJE
  • 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:
    • LN-144
    • Pembrolizumab
  • 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.

Study Arms  ICMJE
  • Experimental: Arm A
    Lifileucel plus Pembrolizumab
    Intervention: Biological: Lifileucel plus Pembrolizumab
  • Active Comparator: Arm B
    Pembrolizumab alone with Optional Crossover Period
    Intervention: Biological: Pembrolizumab with Optional Crossover Period
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 6, 2023)
670
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 1, 2030
Estimated Primary Completion Date March 1, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Iovance Biotherapeutics https://www.tilvance-301.com 1-844-845-4682 Clinical.Inquiries@iovance.com
Contact: Iovance Biotherapeutics Study Team 1-844-845-4682 Clinical.Inquiries@iovance.com
Listed Location Countries  ICMJE Australia,   Canada,   France,   Italy,   Netherlands,   Spain,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05727904
Other Study ID Numbers  ICMJE IOV-MEL-301
TILVANCE-301 ( Other Identifier: Iovance Biotherapeutics, Inc. )
TILVANCE ( Other Identifier: Iovance Biotherapeutics, Inc. )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Iovance Biotherapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Iovance Biotherapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Iovance Biotherapeutics Study Team Iovance Biotherapeutics
PRS Account Iovance Biotherapeutics, Inc.
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP