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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат 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.
• Биопрепарат 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, lif

Первичные конечные точки

• Objective Response Rate and Progression Free Survival [Срок оценки: 5 years total duration]

Вторичные конечные точки (4)

• Overall Survival [Срок оценки: 7 years total duration]
• Complete Response Rate, Duration of Response and Event Free Survival [Срок оценки: 5 years total duration]
• Objective Response Rate, Progression Free Survival, Complete Response Rate, Duration of Responses, Event Free Survival and PFS2 [Срок оценки: 5 years total duration]
• Adverse Events [Срок оценки: 5 years total duration]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 24 центра

• University of Alabama at Birmingham: The Kirklin Clinic — Birmingham
• City of Hope — Duarte
• USC Norris Comprehensive Cancer Center — Los Angeles
• California Pacific Medical Center — San Francisco
• University of Colorado Cancer Center — Aurora
• Orlando Health Cancer Institute — Orlando
• University of Illinois Hospital & Health Sciences System — Chicago
• University of Kansas — Kansas City
• … и ещё 16 центров

Испания · 16 центров

• Hospital Universitario Marques de Valdecilla — Santander
• Hospital Regional Universitario de Malaga - Hospital General — Málaga
• Institut Català d'Oncologia (ICO) — Barcelona
• HM Centro Integral Oncologico Clara Campal — Madrid
• Instituto Oncologico Rosell — Barcelona
• Hospital Universitari Vall dHebron — Barcelona
• Hospital Clinic de Barcelona — Barcelona
• ICO l'Hospitalet - Hospital Duran i Reynals — Barcelona
• … и ещё 8 центров

Италия · 6 центров

• Istituto Romagnolo per lo Studio dei Tumori — Meldola
• Centro di Riferimento Oncologico IRCCS — Aviano
• Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale — Naples
• Azienda Ospedaliero Universitaria Pisana — Pisa
• Istituto Europeo Di Oncologia — Milan
• Azienda Ospedaliera Universitaria Senese — Siena

Великобритания · 6 центров

• Queen Elizabeth Hospital Birmingham — Birmingham
• Freeman Hospital — Newcastle upon Tyne
• Royal Marsden Hospital — Chelsea
• Beaston West of Scotland Canter Centre — Glasgow
• Guy's Hospital — London
• … и ещё 1 центр

Австралия · 5 центров

• Greenslopes Private Hospital — Greenslopes
• Peter MacCallum Cancer Centre — Melbourne
• Fiona Stanley Hospital — Murdoch
• Flinders Medical Centre — Bedford Park
• Westmead Hospital — Westmead

Германия · 5 центров

• Charité - Universitätsmedizin Berlin — Berlin
• Universitätsklinikum Carl Gustav Carus — Dresden
• Universitätsklinikum Hamburg-Eppendorf — Hamburg
• Universitätsklinikum Schleswig-Holstein - Campus Lübeck — Lübeck
• Klinikum Rechts der Isar der Technischen Universität München — Munich

South Korea · 5 центров

• Bundang Medical Center - CHA University — Seongnam-si
• Samsung Medical Center — Seoul
• Korea University Anam Hospital — Seoul
• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul

Франция · 3 центра

• Institut Paoli Calmettes — Marseille
• Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu — Nantes
• Hopital Saint Louis — Paris

Израиль · 3 центра

• Hadassah Medical Center — Jerusalem
• Sheba Medical Center — Ramat Gan
• Tel Aviv Sourasky Medical Center — Tel Aviv

Канада · 2 центра

• Centre hospitalier de l'Université de Montréal — Montreal
• Princess Margaret Cancer Centre — Toronto

Бельгия · 1 центр

• Universitair Ziekenhuis Brussel - Oncologisch Centrum — Jette

Финляндия · 1 центр

• Helsinki University Hospital Comprehensive Cancer Center — Helsinki

Нидерланды · 1 центр

• Nederlands Kanker Instituut — Amsterdam

Сингапур · 1 центр

• National Cancer Centre Singapore — Singapore

Швеция · 1 центр

• Sahlgrenska Universitetssjukhuset — Gothenburg

Швейцария · 1 центр

• Centre Hospitalier Universitaire Vaudois Lausanne — Lausanne

Идентификаторы

NCT: NCT05727904 · IOV-MEL-301 · TILVANCE-301 · TILVANCE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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