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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05727904
• Other study ID #: IOV-MEL-301
• Secondary ID: TILVANCE-301TILV
• Status: Recruiting
• Phase: Phase 3
• Start date: March 30, 2023
• Est. completion date: March 1, 2030

Study information

• Verified date: May 2024
• Source: Iovance Biotherapeutics, Inc.
• Contact: Iovance Biotherapeutics https://www.tilvance-301.com
• Phone: 1-844-845-4682
• Email: Clinical.Inquiries[@]iovance.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 670
• Est. completion date: March 1, 2030
• Est. primary completion date: March 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma
• Unresectable Melanoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Greenslopes Private Hospital	Greenslopes	Queensland
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Canada	Centre hospitalier de l'Université de Montréal	Montréal	Quebec
France	Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu	Nantes
Italy	Istituto Romagnolo per lo Studio dei Tumori	Meldola	Forlì-Cesena
Italy	Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale	Napoli
Netherlands	Nederlands Kanker Instituut	Amsterdam
Spain	Hospital Universitari Vall dHebron	Barcelona
Spain	Instituto Oncologico Rosell	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Universitario Madrid Sanchinarro - CIOCC	Madrid
Spain	Hospital Universitario Quirónsalud Madrid	Madrid
Spain	Hospital Regional Universitario de Malaga - Hospital General	Malaga	Málaga
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Consorcio Hospital General Universitario de Valencia	Valencia
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg	Vastra Gotalands Lan
United States	Baptist Cancer Center	Bartlett	Tennessee
United States	National Cancer Institute	Bethesda	Maryland
United States	University of Alabama at Birmingham: The Kirklin Clinic	Birmingham	Alabama
United States	MD Anderson Cancer Center at Cooper	Camden	New Jersey
United States	University of Virginia	Charlottesville	Virginia
United States	University of Illinois Hospital & Health Sciences System	Chicago	Illinois
United States	Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	St. Luke's Cancer Center - Anderson	Easton	Pennsylvania
United States	University of Kansas	Kansas City	Kansas
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Louisville - James Graham Brown Cancer Center	Louisville	Kentucky
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Iovance Biotherapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Italy,  Netherlands,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	5 years total duration
Secondary	Overall Survival	To compare the efficacy of lifileucel plus pembrolizumab with the efficacy of pembrolizumab alone measured by overall survival (OS)	7 years total duration
Secondary	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	5 years total duration
Secondary	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	5 years total duration
Secondary	Adverse Events	To characterize the safety and tolerability profile of lifileucel plus pembrolizumab and pembrolizumab alone in participants with unresectable or metastatic melanoma	5 years total duration