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

Primary Purpose

Metastatic Melanoma, Unresectable Melanoma, Melanoma

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Lifileucel plus Pembrolizumab
Pembrolizumab with Optional Crossover Period
Sponsored by
Iovance Biotherapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Melanoma focused on measuring 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

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participant has a histologically or pathologically confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma. 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. Participant is assessed as having at least one resectable lesion (or aggregate lesions) for lifileucel generation. Participant must have at least one measurable disease as defined by RECIST 1.1 following tumor resection. Participants must have adequate organ function. Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control. Participants who are > 70 years of age may be allowed to enroll after the investigator discusses with the medical monitor. Exclusion Criteria: Participant has melanoma of uveal/ocular origin. Participant has symptomatic untreated brain metastases. Participant received more than 1 prior line of therapy. Participant received prior therapy for metastatic disease Participants with a BRAF V600 mutation-positive tumor received prior adjuvant/neoadjuvant ICI therapy only 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. Participant has any form of primary or acquired immunodeficiency (eg, SCID or AIDS). 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.) Participant has a history of allogeneic cell or organ transplant. Other protocol defined inclusion/exclusion criteria could apply.

Sites / Locations

  • USC Norris Comprehensive Cancer CenterRecruiting
  • Orlando Health Cancer InstituteRecruiting
  • MD Anderson Cancer Center at CooperRecruiting
  • Allegheny Health NetworkRecruiting
  • Baptist Cancer CenterRecruiting
  • Greenslopes Private HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

Lifileucel plus Pembrolizumab

Pembrolizumab alone with Optional Crossover Period

Outcomes

Primary Outcome Measures

Objective Response Rate and Progression Free Survival
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

Overall Survival
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
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
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
To characterize the safety and tolerability profile of lifileucel plus pembrolizumab and pembrolizumab alone in participants with unresectable or metastatic melanoma

Full Information

First Posted
February 6, 2023
Last Updated
October 16, 2023
Sponsor
Iovance Biotherapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05727904
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 30, 2023 (Actual)
Primary Completion Date
March 1, 2028 (Anticipated)
Study Completion Date
March 1, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Iovance Biotherapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
670 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Lifileucel plus Pembrolizumab
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Pembrolizumab alone with Optional Crossover Period
Intervention Type
Biological
Intervention Name(s)
Lifileucel plus Pembrolizumab
Other Intervention Name(s)
LN-144, Pembrolizumab
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab with Optional Crossover Period
Intervention Description
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.
Primary Outcome Measure Information:
Title
Objective Response Rate and Progression Free Survival
Description
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
Time Frame
5 years total duration
Secondary Outcome Measure Information:
Title
Overall Survival
Description
To compare the efficacy of lifileucel plus pembrolizumab with the efficacy of pembrolizumab alone measured by overall survival (OS)
Time Frame
7 years total duration
Title
Complete Response Rate, Duration of Response and Event Free Survival
Description
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
Time Frame
5 years total duration
Title
Objective Response Rate, Progression Free Survival, Complete Response Rate, Duration of Responses, Event Free Survival and PFS2
Description
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
Time Frame
5 years total duration
Title
Adverse Events
Description
To characterize the safety and tolerability profile of lifileucel plus pembrolizumab and pembrolizumab alone in participants with unresectable or metastatic melanoma
Time Frame
5 years total duration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participant has a histologically or pathologically confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma. 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. Participant is assessed as having at least one resectable lesion (or aggregate lesions) for lifileucel generation. Participant must have at least one measurable disease as defined by RECIST 1.1 following tumor resection. Participants must have adequate organ function. Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control. Participants who are > 70 years of age may be allowed to enroll after the investigator discusses with the medical monitor. Exclusion Criteria: Participant has melanoma of uveal/ocular origin. Participant has symptomatic untreated brain metastases. Participant received more than 1 prior line of therapy. Participant received prior therapy for metastatic disease Participants with a BRAF V600 mutation-positive tumor received prior adjuvant/neoadjuvant ICI therapy only 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. Participant has any form of primary or acquired immunodeficiency (eg, SCID or AIDS). 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.) Participant has a history of allogeneic cell or organ transplant. Other protocol defined inclusion/exclusion criteria could apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Iovance Biotherapeutics https://www.tilvance-301.com
Phone
1-844-845-4682
Email
Clinical.Inquiries@iovance.com
First Name & Middle Initial & Last Name or Official Title & Degree
Iovance Biotherapeutics Study Team
Phone
1-844-845-4682
Email
Clinical.Inquiries@iovance.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Iovance Biotherapeutics Study Team
Organizational Affiliation
Iovance Biotherapeutics
Official's Role
Study Director
Facility Information:
Facility Name
USC Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90007
Country
United States
Individual Site Status
Recruiting
Facility Name
Orlando Health Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Individual Site Status
Recruiting
Facility Name
MD Anderson Cancer Center at Cooper
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Individual Site Status
Recruiting
Facility Name
Allegheny Health Network
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Recruiting
Facility Name
Baptist Cancer Center
City
Bartlett
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Individual Site Status
Recruiting
Facility Name
Greenslopes Private Hospital
City
Greenslopes
State/Province
Queensland
ZIP/Postal Code
4120
Country
Australia
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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