Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer

Official title

A Phase 2 Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (TIL or LN-145) in Patients With Metastatic Non-Small-Cell Lung Cancer

Overview

This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic non-small-cell lung cancer

Detailed description

LN-145 is a ready-to-infuse TIL therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI and further optimized by Iovance for the treatment of patients with metastatic NSCLC. The cell transfer therapy used in this study involves patients receiving a non-myeloablative (NMA) lymphodepleting preparative regimen, followed by infusion of autologous TIL, then finally followed by the administration of IL-2.

Interventions

• Biological LN-145
  A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145), followed by IL-2.
• Biological LN-145
  A tumor sample is obtained by image-guided core biopsy from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145) followed by IL-2.

Primary outcome measures

• Objective Response Rate [Time frame: Up to 60 months]

Secondary outcome measures (8)

• Objective Response Rate [Time frame: Up to 60 months]
• Complete Response Rate [Time frame: Up to 60 months]
• Duration of Response [Time frame: Up to 60 months]
• Disease Control Rate [Time frame: Up to 60 months]
• Progression-Free Survival [Time frame: Up to 60 months]
• Overall Survival [Time frame: Up to 60 months]
• Adverse Events [Time frame: Up to 60 months]
• Core Biopsies [Time frame: Up to 60 months]

Eligibility criteria

Inclusion criteria

• Patients who are over 70 years of age may be allowed to enroll after discussion with the Medical Monitor.
• Have historically or pathologically confirmed diagnosis of metastatic Stage IV NSCLC without EGFR, ALK, or ROS1 genomic alterations.
• For patients who have actionable mutations (other than EGFR, ALK, or ROS1 genomic alterations), 1 additional line of therapy with the appropriate health authority approved targeted therapy is required.
• Patients must have documented radiographic disease progression on or after the first-line therapy, including concurrent or sequential ICI and platinum-based chemotherapy ± bevacizumab. No more than 1 prior line is allowed if ICI and platinum-based chemotherapy were administered concurrently and no more than 2 prior lines are allowed for sequential administration of platinum-based chemotherapy and ICI as 2 separate lines.
• LN-145 manufacture is allowed for patients who have residual resectable disease after completion of the platinum-based chemotherapy component of the front-line ICI and platinum-based chemotherapy combination and meet all eligibility criteria except documented disease progression. These patients must intend to receive TIL therapy after disease progression
• Prior systemic therapy in the adjuvant or neoadjuvant setting, or as part of definitive chemoradiotherapy, will count as a line of therapy if the patient had disease progression during or within 12 months after the completion of such therapy.
• At least 1 resectable lesion for TIL production and at least one remaining measurable lesion, as defined by RECIST v1.1
• Have adequate organ function
• LVEF > 45%, NYHA Class 1
• Have adequate pulmonary function
• ECOG performance status of 0 or 1
• Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and up to 12 months after all protocol-related therapy

Exclusion criteria

• Patients who have EGFR, ALK or ROS1 driver mutations
• Patients who have symptomatic, untreated brain metastases.
• Patients who have had allogeneic organ transplant or prior cell therapy within the past 20 years
• Patients who have any form of primary immunodeficiency
• Patients who are on systemic steroid therapy ≥ 10 mg/day of prednisone or equivalent.
• Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment
• Patients who have had another primary malignancy within the previous 3 years
• Participation in another interventional clinical study within 21 days

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 27 centers

• Banner Health MD Anderson — Gilbert
• Sylvester Comprehensive Cancer Center — Miami
• H Lee Moffitt Cancer Center and Research Institute — Tampa
• Rush University Medical Center — Chicago
• University of Illinois Hospital & Health Sciences System — Chicago
• Advocate Aurora Health — Park Ridge
• University of Louisville — Louisville
• University of Maryland — Baltimore
• … and 19 more centers

Spain · 14 centers

• Hospital Universitario A Coruña — A Coruña
• Instituto Oncologico Rosell — Barcelona
• Hospital Clinic de Barcelona — Barcelona
• C.H. Regional Reina Sofia — Córdoba
• Hospital Universitario Ramon y Cajal — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitario La Paz — Madrid
• Hospital Universitario Madrid Sanchinarro - Centro Integral Oncologico Clara Campal — Madrid
• … and 6 more centers

France · 6 centers

• Institut Paoli Calmettes — Marseille
• CHU Nantes — Nantes
• CHU Nice — Nice
• Centre Hospitalier Lyon Sud — Pierre-Bénite
• CHRU de Poitiers La Miletrie — Poitiers
• Gustave Roussy Cancer Campus — Villejuif

United Kingdom · 6 centers

• Royal Marsden Hospital — Chelsea
• Sarah Cannon Research Institute — London
• University College London — London
• The Christie NHS Foundation Trust — Manchester
• Queen Elizabeth Hospital Birmingham — Birmingham
• Guy's Hospital — London

Germany · 4 centers

• Charite- Universitätsklinikum Berlin — Berlin
• Universitätsklinikum Carl Gustav Carus, MK I — Dresden
• Universitätsklinikum Frankfurt — Frankfurt
• Universitätsklinikum Mannheim — Mannheim

Italy · 4 centers

• Azienda Ospedaliera Universitaria Careggi — Florence
• Fondazione IRCCS Policlinico San Matteo di Pavia — Pavia
• Azienda Ospedaliera Ospedali Riuniti Marche Nord — Pesaro
• IRCCS Fondazione del Piemonte per l'Oncologia — Piemonte

Australia · 3 centers

• St. Vincent's Hospital — Darlinghurst
• Westmead Hospital — Westmead
• Hollywood Private Hospital Ramsay — Nedlands

South Korea · 3 centers

• Samsung Medical Center — Seoul
• Gachon Unversity Gil Medical Center — Incheon
• Severance Hospital, Yonsei University — Seoul

Canada · 1 center

• Centre Hospitalier de l'Universite de Montreal (CHUM) — Montreal

Netherlands · 1 center

• Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis — Amsterdam

Singapore · 1 center

• National Cancer Centre Singapore — Singapore

Switzerland · 1 center

• Centre Hospitalier Universitaire Vaudois Lausanne — Lausanne

Identifiers

NCT: NCT04614103 · IOV-LUN-202 · 2020-003629-45 · 2024-510778-26-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗