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

Metastatic Non Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04614103
• Other study ID #: IOV-LUN-202
• Secondary ID: 2020-003629-4520
• Status: Recruiting
• Phase: Phase 2
• Start date: May 7, 2021
• Est. completion date: December 2031

Study information

• Verified date: May 2024
• Source: Iovance Biotherapeutics, Inc.
• Contact: Iovance Biotherapeutics Study Team lungcelltherapy.com
• Phone: 1-844-845-4682
• Email: Clinical.Inquiries[@]iovance.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: December 2031
• Est. primary completion date: December 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Non Small Cell Lung Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montréal
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Germany	Universitätsklinikum Carl Gustav Carus, MK I	Dresden
Netherlands	Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam
Switzerland	University Hospital of Zurich/ Universitätsspital Zürich	Zürich
United States	Augusta University	Augusta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	MD Anderson Cooper	Camden	New Jersey
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Novant Health - Charlotte	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois Hospital & Health Sciences System	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	University of Florida Health Cancer Center	Gainesville	Florida
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	University of Southern California	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Baptist Cancer Center	Memphis	Tennessee
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Allegheny General Hospital	Natrona Heights	Pennsylvania
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	Christiana Care Health System	Newark	Delaware
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	AdventHealth Cancer Institute	Orlando	Florida
United States	Advocate Aurora Health	Park Ridge	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	VCU Medical Center (Virginia Commonwealth University)	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Avera Medical Group Cancer Institute	Sioux Falls	South Dakota
United States	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Atrium Health Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Novant Health - Winston-Salem	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Iovance Biotherapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	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	Up to 60 months
Secondary	Objective Response Rate	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	Up to 60 months
Secondary	Complete Response Rate	To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1	Up to 60 months
Secondary	Duration of Response	To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1	Up to 60 months
Secondary	Disease Control Rate	To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1	Up to 60 months
Secondary	Progression-Free Survival	To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1	Up to 60 months
Secondary	Overall Survival	To evaluate efficacy parameters such as Overall Survival (OS)	Up to 60 months
Secondary	Adverse Events	To characterize the safety profile of LN-145 in patients with non-small-cell lung cancer (NSCLC)	Up to 60 months
Secondary	Core Biopsies	To determine the feasibility of generating LN-145 using tumor tissue obtained via image-guided core biopsy	Up to 60 months