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

3. november 2026 opdateret af: 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.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

10

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

  • Forenede Stater
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02115
      • Boston, Massachusetts, Forenede Stater, 02115
      • Boston, Massachusetts, Forenede Stater, 02115
        • Beth Israel Deaconess Medical Center (BIDMC)
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ja

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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
Medicin: Cyclophosphamide

Part of the lymphodepleting chemotherapy given before LN-145 infusion

Medicin: Fludarabine

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

Medicin: Aldesleukin (IL-2)

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

Procedure: Tumor Resection

Surgical removal of tumor tissue for TIL production/manufacture

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Radiographic Objective Response Rate
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Radiographic change in target lesions
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Beth Israel Deaconess Medical Center

Samarbejdspartnere

Iovance Biotherapeutics, Inc.

Efterforskere

  • Ledende efterforsker: David Einstein, MD, Beth Israel Deaconess Medical Center

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

26. april 2027

Primær færdiggørelse (Anslået)

1. august 2029

Studieafslutning (Anslået)

1. marts 2030

Datoer for studieregistrering

Først indsendt

28. oktober 2026

Først indsendt, der opfyldte QC-kriterier

3. november 2026

Først opslået (Faktiske)

9. november 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

9. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

3. november 2026

Sidst verificeret

1. november 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 26-686

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

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.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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