Clinical trial NCT04614103: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Non Small Cell Lung Cancer
Keywords: LN-145
Cell Therapy
Autologous Adoptive Cell Therapy
Cellular Immuno-therapy
Tumor Infiltrating Lymphocytes
TIL
IL-2
Non Small Cell Lung Cancer
NSCLC
Second line Lung Cancer
Bronchial Neoplasms
Carcinoma
Lung Disease
Metastatic Lung Cancer
Metastatic Non Small Cell Lung Cancer
Metastatic NSCLC
Lung Carcinoma
PD-L1
Stage IV Lung Cancer
Stage IV Non-Small Cell Lung Cancer
Stage IV NSCLC
Systemic Therapy
2nd line therapy
Second line therapy
CPI
Immune checkpoint inhibitor (ICI)
NSCLC Recurrent
Recurrent Lung Cancer
Recurrent Lung Carcinoma
Lead sponsor: Iovance Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-11-03
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Objective Response Rate
timeFrame: Up to 60 months
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Up to 60 months
measure: Complete Response Rate
timeFrame: Up to 60 months
measure: Duration of Response
timeFrame: Up to 60 months
measure: Disease Control Rate
timeFrame: Up to 60 months
measure: Progression-Free Survival
timeFrame: Up to 60 months
measure: Overall Survival
timeFrame: Up to 60 months
measure: Adverse Events
timeFrame: Up to 60 months
measure: Core Biopsies
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Newark
country: United States
facility: Christiana Care Health System
state: Delaware
city: Gainesville
country: United States
facility: University of Florida Health Cancer Center
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Cancer Institute
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Hospital & Health Sciences System
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Aurora Health
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Camden
country: United States
facility: MD Anderson Cooper
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health - Charlotte
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health - Winston-Salem
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Natrona Heights
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Medical Group Cancer Institute
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Memphis
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Richmond
country: United States
facility: VCU Medical Center (Virginia Commonwealth University)
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Nedlands
country: Australia
facility: Hollywood Private Hospital Ramsay
state: Western Australia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus, MK I
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu
city: Incheon
country: Korea, Republic of
facility: Gachon Unversity Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois Lausanne
state: Vaud
city: Zürich
country: Switzerland
facility: University Hospital of Zurich/ Universitätsspital Zürich
city: Chelsea
country: United Kingdom
facility: Royal Marsden Hospital
state: England
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
state: England
city: London
country: United Kingdom
facility: University College London
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
Study officials:
affiliation: Iovance Biotherapeutics
name: Iovance Biotherapeutics Study Team
role: STUDY_DIRECTOR
References: