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

Phase 3

Recruiting

• Conditions: Melanoma; Unresectable Melanoma; Metastatic Melanoma
• Interventions: Biological: Lifileucel plus Pembrolizumab; Biological: Pembrolizumab with Optional Crossover Period

• Registration Number: NCT05727904
• Lead Sponsor: Iovance Biotherapeutics, Inc.

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 Timeline

• Study First Submitted: 2023-02-06
• Study First Submitted QC: 2023-02-06
• Study First Posted: 2023-02-14
• Study Start: 2023-03-30
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-07
• Last Update Posted: 2025-07-08
• Primary Completion: 2028-03-01
• Study Completion: 2030-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 670

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Lifileucel plus Pembrolizumab	Lifileucel plus Pembrolizumab
Arm B	Pembrolizumab with Optional Crossover Period	Pembrolizumab alone with Optional Crossover Period

Primary Outcome Measures

Name	Time	Method
Objective Response Rate and Progression Free Survival	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

Name	Time	Method
Complete Response Rate, Duration of Response and Event Free Survival	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	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
Overall Survival	7 years total duration	To compare the efficacy of lifileucel plus pembrolizumab with the efficacy of pembrolizumab alone measured by overall survival (OS)
Adverse Events	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

Trial Locations

Locations (72)

University of Alabama at Birmingham: The Kirklin Clinic; 🇺🇸 Birmingham, Alabama, United States

City of Hope; 🇺🇸 Duarte, California, United States

USC Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Orlando Health Cancer Institute; 🇺🇸 Orlando, Florida, United States

University of Illinois Hospital & Health Sciences System; 🇺🇸 Chicago, Illinois, United States

University of Kansas; 🇺🇸 Kansas City, Kansas, United States

University of Louisville - James Graham Brown Cancer Center; 🇺🇸 Louisville, Kentucky, United States

National Cancer Institute; 🇺🇸 Bethesda, Maryland, United States

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