Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer
- Registration Number
- NCT04614103
- Lead Sponsor
- Iovance Biotherapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 170
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 LN-145 Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) \< 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression Retreatment Cohort LN-145 Patients who were previously treated with LN-145 in Cohort 1, 2, 3, or 4. Cohort 2 LN-145 Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment Cohort 3 LN-145 Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation Cohort 4 LN-145 Patients, regardless of tumor PD-L1 expression status prior to ICI treatment, who have meet all inclusion/exclusion criteria except the requirement to have documented disease progression may elect to have the tumor harvest procedure and TIL production prior to disease progression on their current anticancer treatment. Documentation of progressive disease and identification of a target lesion for RECIST v1.1 assessment is required at Baseline for these patients.
- Primary Outcome Measures
Name Time Method Objective Response Rate Up to 60 months To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) in patients with metastatic NSCLC using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as assessed by central review for Cohorts 1 and 2 and by the investigator for Cohorts 3, 4 and the Retreatment Cohort
- Secondary Outcome Measures
Name Time Method Disease Control Rate Up to 60 months To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1
Core Biopsies Up to 60 months To determine the feasibility of generating LN-145 using tumor tissue obtained via image-guided core biopsy
Objective Response Rate Up to 60 months To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) per RECIST v1.1, as assessed by the Investigator for Cohorts 1 and 2
Complete Response Rate Up to 60 months To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1
Duration of Response Up to 60 months To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1
Progression-Free Survival Up to 60 months To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1
Adverse Events Up to 60 months To characterize the safety profile of LN-145 in patients with non-small-cell lung cancer (NSCLC)
Overall Survival Up to 60 months To evaluate efficacy parameters such as Overall Survival (OS)
Trial Locations
- Locations (60)
City of Hope
🇺🇸Duarte, California, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Christiana Care Health System
🇺🇸Newark, Delaware, United States
University of Florida Health Cancer Center
🇺🇸Gainesville, Florida, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
AdventHealth Cancer Institute
🇺🇸Orlando, Florida, United States
H Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Illinois Hospital & Health Sciences System
🇺🇸Chicago, Illinois, United States
Advocate Aurora Health
🇺🇸Park Ridge, Illinois, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
MD Anderson Cooper
🇺🇸Camden, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
New York University Langone Medical Center
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Novant Health - Charlotte
🇺🇸Charlotte, North Carolina, United States
Novant Health - Winston-Salem
🇺🇸Winston-Salem, North Carolina, United States
Atrium Health Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Allegheny General Hospital
🇺🇸Natrona Heights, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Avera Medical Group Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Baptist Cancer Center
🇺🇸Memphis, Tennessee, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Houston Methodist
🇺🇸Houston, Texas, United States
VCU Medical Center (Virginia Commonwealth University)
🇺🇸Richmond, Virginia, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
St. Vincent's Hospital
🇦🇺Darlinghurst, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Hollywood Private Hospital Ramsay
🇦🇺Nedlands, Western Australia, Australia
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM)
🇨🇦Montréal, Canada
Universitätsklinikum Carl Gustav Carus, MK I
🇩🇪Dresden, Germany
Universitätsklinikum Mannheim
🇩🇪Mannheim, Germany
Samsung Medical Center
🇰🇷Seoul, Gangnam-gu, Korea, Republic of
Gachon Unversity Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Severance Hospital, Yonsei University
🇰🇷Seoul, Korea, Republic of
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
Centre Hospitalier Universitaire Vaudois Lausanne
🇨🇭Lausanne, Vaud, Switzerland
University Hospital of Zurich/ Universitätsspital Zürich
🇨🇭Zürich, Switzerland
Royal Marsden Hospital
🇬🇧Chelsea, England, United Kingdom
Sarah Cannon Research Institute
🇬🇧London, England, United Kingdom
University College London
🇬🇧London, England, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom