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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 : April 30, 2024
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Unresectable Melanoma Melanoma Biological: Lifileucel plus Pembrolizumab Biological: Pembrolizumab with Optional Crossover Period Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 670 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 30, 2023
Estimated Primary Completion Date : March 1, 2028
Estimated Study Completion Date : March 1, 2030

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
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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:
  • LN-144
  • Pembrolizumab
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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

  4. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05727904


Contacts
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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

Locations
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Sponsors and Collaborators
Iovance Biotherapeutics, Inc.
Investigators
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Study Director: Iovance Biotherapeutics Study Team Iovance Biotherapeutics
More Information
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Responsible Party: Iovance Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05727904    
Other Study ID Numbers: IOV-MEL-301
TILVANCE-301 ( Other Identifier: Iovance Biotherapeutics, Inc. )
TILVANCE ( Other Identifier: Iovance Biotherapeutics, Inc. )
First Posted: February 14, 2023    Key Record Dates
Last Update Posted: April 30, 2024
Last Verified: April 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Iovance Biotherapeutics, Inc.:
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
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
 Skin Neoplasms
Neoplasms by Site
Skin Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action