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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
670
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.
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.
University of Alabama at Birmingham: The Kirklin Clinic
Birmingham, Alabama, United States
RECRUITINGCity of Hope
Duarte, California, United States
RECRUITINGUSC Norris Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGCalifornia Pacific Medical Center
San Francisco, California, United States
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
Time frame: 5 years total duration
Overall Survival
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
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
Time frame: 5 years total duration
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
Time frame: 5 years total duration
Adverse Events
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
Iovance Biotherapeutics https://www.tilvance-301.com
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University of Colorado Cancer Center
Aurora, Colorado, United States
RECRUITINGOrlando Health Cancer Institute
Orlando, Florida, United States
RECRUITINGUniversity of Illinois Hospital & Health Sciences System
Chicago, Illinois, United States
RECRUITINGUniversity of Kansas
Kansas City, Kansas, United States
RECRUITINGUniversity of Louisville - James Graham Brown Cancer Center
Louisville, Kentucky, United States
RECRUITINGNational Cancer Institute
Bethesda, Maryland, United States
RECRUITING...and 62 more locations