Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

Lifileucel (TIL) Therapy After PD-1 Blockade Failure in Kidney Cancer

3 novembre 2026 mis à jour par: David J. Einstein, Beth Israel Deaconess Medical Center

A Phase II Trial of Autologous Ex Vivo Expanded Tumor-Infiltrating Lymphocyte (TIL) Therapy With Lifileucel After Failure of PD-1 Blockade in Kidney Cancer.

This study aims to evaluate autologous ex vivo expanded tumor-infiltrating lymphocyte therapy (lifileucel/LN-145) for kidney cancer after failure of PD-1 blockade.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Description détaillée

This is a Phase II single-arm trial of tumor-infiltrating lymphocyte (TIL) therapy in kidney cancer. Briefly, participants who meet eligibility criteria undergo surgical removal of a metastasis or primary tumor to provide material for generation of the TIL product in a lab, which involves growing and expanding the immune cells contained in the tumor before infusing the TIL product into the patient.

Baseline evaluations occur before tumor harvest, and participants who proceed on study undergo tumor resection so tissue can be shipped to a manufacturing facility to create the autologous TIL product LN-145/lifileucel. The treatment plan includes 5 days of lymphodepleting chemotherapy before TIL infusion, using cyclophosphamide and fludarabine, followed by LN-145 infusion on Day 0 and IL-2 (aldesleukin) afterward. The study calendar includes post-treatment visits around Day 14, Day 28, Weeks 8, 12, and 18, then every 3 months starting at Month 6, with long-term follow-up by telephone continuing until study end or withdrawal, up to Month 36. Participants undergo screening and tumor resection to obtain tissue for manufacture of the TIL product. If treatment proceeds, participants receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by LN-145 infusion and IL-2 (aldesleukin). Participants complete scheduled clinic-based assessments and longer-term follow-up, including telephone follow-up approximately every 3 months for up to about 3 years

Type d'étude

Interventionnel

Inscription (Estimé)

10

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • États-Unis
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02115
      • Boston, Massachusetts, États-Unis, 02115
      • Boston, Massachusetts, États-Unis, 02115
        • Beth Israel Deaconess Medical Center (BIDMC)
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Histologically or cytologically confirmed, advanced or metastatic renal cell carcinoma with clear cell, papillary, sarcomatoid (with or without other subtypes present), or unclassified histology. Other non-clear cell subtypes are also eligible if the patient has had a prior documented response to immune checkpoint inhibitor therapy.

    • Participants must have measurable disease with at least two malignant lesions, one for disease monitoring as response to therapy and one for TIL harvest.
    • Age ≥18 years
    • Received one of the following regimens:
    • Anti-PD-(L)1 immune checkpoint inhibitor (ICI) with or without an anti-CTLA-4 ICI or VEGF tyrosine kinase inhibitor (TKI) for treatment of advanced/metastatic disease, and experienced either (1) radiographic progression of disease while on treatment or (2) best response of stable disease after at least 6 months
    • Adjuvant anti-PD-(L)1 ICI after nephrectomy for localized disease and had either (1) disease recurrence while receiving adjuvant ICI or (2) disease recurrence within 6 months of the final dose of any amount of adjuvant ICI
    • Prior HIF2α inhibitor exposure in the adjuvant or advanced/metastatic setting is allowed but not required
    • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of ≥ 3 months in the opinion of the Investigator.
    • Participants must have adequate organ and marrow function as defined in the protocol.
    • Patients with definitively treated brain metastases may be considered for enrollment if the patient is clinically stable for ≥ 14 days, with no lesions on follow-up imaging and no requirement for ongoing steroid treatment.
    • Participants must have a washout period from any anticancer therapy prior to tumor harvest. The protocol contains provisions for optional use of "bridging" TKI between tumor harvest and lymphodepleting chemotherapy.
    • Palliative radiation therapy is permitted as long as it does not involve lesions being selected for resection for TIL manufacturing, or being assessed radiographically as target lesions.
    • Participants must have recovered from all prior anti-cancer therapy-related adverse events (AEs), as defined in the protocol.
    • Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control.
    • Previous surgical procedure(s) is/are permitted provided that wound healing has occurred, all complications have resolved, and at least 14 days have elapsed (for major operative procedures) prior to the tumor resection.

Exclusion Criteria:

  • Patients who have received an organ allograft or prior cell transfer therapy within the past 20 years that included a non-myeloablative or myeloablative chemotherapy regimen.
  • Patients who have a history of hypersensitivity to any component of the study intervention.
  • Patients with rapidly progressive disease or symptomatic disease requiring urgent treatment per investigator discretion.
  • Patients with symptomatic and/or untreated brain metastases.
  • Patients who are on chronic systemic steroid therapy except for those requiring steroid therapy for management of adrenal insufficiency.
  • Patients who are pregnant or breastfeeding.
  • Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency disease [SCID] and acquired immunodeficiency syndrome [AIDS]).
  • Patients with any other primary malignancy that is radiographically visible or is expected to require treatment within the next three years.
  • Patients who are hypoxemic (oxygen saturation <90%) on room air at baseline or who require supplemental oxygen.

Other protocol-defined inclusion/exclusion criteria may apply.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Lifileucel (LN-145) TIL regimen

Participants undergo tumor resection for TIL manufacturing, then receive lymphodepleting cyclophosphamide and fludarabine, followed byLN-145/lifileucel infusion and IL-2 (aldesleukin), with scheduled post-treatment clinic visits and long-term follow-up
Médicament: Cyclophosphamide

Part of the lymphodepleting chemotherapy given before LN-145 infusion

Médicament: Fludarabine

Part of the lymphodepleting chemotherapy given before LN-145 infusion.

Médicament: Aldesleukin (IL-2)

Administered after LN-145 infusion as part of the treatment regimen.

Procédure: Tumor Resection

Surgical removal of tumor tissue for TIL production/manufacture

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Radiographic Objective Response Rate
Délai: Participants will be followed thought out the course of the trial for 3 years

HCC-centrally assessed Objective Response Rate per RECIST 1.1 of the efficacy evaluable population Primary analysis is performed on patients who receive TIL.
Participants will be followed thought out the course of the trial for 3 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Radiographic change in target lesions
Délai: Participants will be followed thought out the course of the trial for 3 years

Longitudinal and best change in target lesion measurements. Target lesions are measured at baseline and followed per RECIST 1.1
Participants will be followed thought out the course of the trial for 3 years
Radiographic Disease Control Rate (SD + PR + CR)
Délai: Participants will be followed thought out the course of the trial for 3 years

Disease control rate is listed as a secondary endpoint and will be summarized in the efficacy cohort.
Participants will be followed thought out the course of the trial for 3 years
Duration of response
Délai: Participants will be followed thought out the course of the trial for 3 years

Duration of overall response is measured from the first time CR or PR criteria are met until the first date recurrent or progressive disease is objectively documented, or death due to any cause
Participants will be followed thought out the course of the trial for 3 years
Progression-free survival
Délai: Participants will be followed thought out the course of the trial for 3 years

Progression-free survival is a listed secondary endpoint for both the efficacy evaluable population and the total population. Time-to-event variables are calculated from TIL infusion; PFS is also calculated for the total population from trial enrollment.
Participants will be followed thought out the course of the trial for 3 years
Toxicity per CTCAE v6.0
Délai: Participants will be followed thought out the course of the trial for 3 years

Adverse events are graded using NCI Common Terminology Criteria for Adverse Events version 6.0.
Participants will be followed thought out the course of the trial for 3 years
Feasibility
Délai: Assessed at time of TIL infusion (D0)

Feasibility is defined as the proportion of patients who successfully undergo tumor harvest, ex vivo TIL expansion, lymphodepletion, and TIL infusion, regardless of number of IL-2 doses given post-TIL.
Assessed at time of TIL infusion (D0)

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Beth Israel Deaconess Medical Center

Collaborateurs

Iovance Biotherapeutics, Inc.

Les enquêteurs

  • Chercheur principal: David Einstein, MD, Beth Israel Deaconess Medical Center

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

26 avril 2027

Achèvement primaire (Estimé)

1 août 2029

Achèvement de l'étude (Estimé)

1 mars 2030

Dates d'inscription aux études

Première soumission

28 octobre 2026

Première soumission répondant aux critères de contrôle qualité

3 novembre 2026

Première publication (Réel)

9 novembre 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

9 novembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

3 novembre 2026

Dernière vérification

1 novembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 26-686

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

The Harvard Cancer Consortium encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE
  • SÈVE

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

S'abonner