Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03645928
• Other study ID #: IOV-COM-202
• Secondary ID: 2018-001608-12
• Status: Recruiting
• Phase: Phase 2
• Start date: May 7, 2019
• Est. completion date: August 9, 2029

Study information

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

Clinical Trial Summary

A prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL LN-144 (Lifileucel)/LN-145 in combination with checkpoint inhibitors or TIL LN-144 (Lifileucel)/LN-145/LN-145-S1 as a single agent therapy.

Description:

LN-144 (Lifileucel)/LN-145/LN-145-S1 is an adoptive cell transfer therapy that utilizes an autologous TIL for the treatment of patients with unresectable or metastatic melanoma, advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, and locally advanced or metastatic non-small cell lung cancer. The adoptive cell transfer therapy used in this study involves patients receiving a nonmyeloablative (NMA) lymphodepletion regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2. Patients in Cohorts 1A, 2A, 3A and 3C will receive TIL plus checkpoint inhibitors. Patients in Cohorts 1B, 1C, and 3B will receive autologous TIL as a single therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 178
• Est. completion date: August 9, 2029
• Est. primary completion date: August 9, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria

• Must have a confirmed diagnosis of malignancy of their receptive histologies:

unresectable or metastatic melanoma Stage IIIC to IV (Cohorts 1A,1B and 1C), advanced, recurrent or metastatic HNSCC (Cohort 2A), or Stage III or Stage IV non-small cell lung cancer (Cohorts 3A, 3B, and 3C).

• Cohorts 1A, 2A, and 3A: If previously treated, patients must have progressed on or after most recent therapy and must not have received CPIs as part of one of the counted lines of prior therapy. Patients must have radiologically documented disease progression while receiving or after the completion of the most recent prior treatment. Patients may have received up to 3 prior systemic anticancer therapies (except for Cohort 3A, where patients whose tumors harbor actionable mutations may have received up to 4 prior systemic therapies)

• Cohorts 1B, 1C, 3B, and 3C: Unresectable or metastatic melanoma patients in Cohorts 1B or 1C must have previously received systemic therapy with a PD-1 blocking antibody. NSCLC patients in Cohort 3B must have previously received systemic therapy with any CPI (except for those patients with known oncogene driver mutations that are sensitive to targeted therapies) as part of 1 - 3 prior lines of therapy. NSCLC patients in Cohort 3C must have previously received 1 line of CPI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neoadjuvant settings are allowed.

• Must have at least 1 resectable lesion

• Must have remaining measurable disease as defined by RECIST 1.1 following tumor resection

• Must be = 18 years at the time of consent for Cohorts 1A, 1C, 2A, 3A, 3B, and 3C. Patients must be = 12 years at the time of consent for Cohort 1B. Enrollment of patients > 70 years of age may be allowed after consultation with the Medical Monitor.

• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and an estimated life expectancy of = 6 months.

• Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of birth control during treatment and for 12 months after their last dose of IL-2, 4 months after their last dose of pembrolizumab, or 5 months after their last dose of ipilimumab or nivolumab, whichever occurs later.

Exclusion Criteria

• Patients with melanoma of uveal/ocular origin.

• Patients who have a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years. Patients being retreated with TIL, as part of this study are not excluded.

• Patients who have symptomatic, untreated brain metastases

• Patients who are on systemic steroid therapy > 10 mg/day of prednisone or other steroid equivalent. Patients receiving steroids as replacement therapy for adrenocortical insufficiency at = 10 mg/day of prednisone or other steroid equivalent may be eligible.

• Patients who are pregnant or breastfeeding.

• Patients who have an active medical illness(es), which in the opinion of the Investigator, would pose increased risks for study participation

• Cohort 1A, 2A, 3A, and 3C patients may not have a medical history of autoimmune disorders (including pneumonitis) requiring treatment or active management.

• Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment

• Patients who have any form of primary immunodeficiency

• Patients with a history of hypersensitivity to any component of the study drugs

• Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association Class II or higher

• Patients with respiratory dysfunction or history of smoking are excluded if not meeting either of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.7 or FEV1 > 50%.

• Patients who have had another primary malignancy within the previous 3 years

• Participation in another interventional clinical study within 21 days prior to the initiation of treatment.

Related Conditions & MeSH terms

• Metastatic Melanoma
• Non-small Cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck

Intervention

Biological:
• Lifileucel
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with Lifileucel followed by IL-2 administration. Lifileucel will be administered to patients once (on Day 0) during the study.
• LN-145
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration. TIL will be administered to patients once (on Day 0) during the study.

Drug:
• Pembrolizumab
Humanized antibody. Pembrolizumab will be administered following tumor resection and will continue every 3 weeks or every 6 weeks thereafter for up to 2 years.

Biological:
• LN-145-S1
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145-S1) followed by IL-2 administration. TIL will be administered to patients once (on Day 0) during the study.

Drug:
• Ipilimumab
Monoclonal antibody Ipilimumab will be administered as a single dose prior to tumor resection.
• Nivolumab
Monoclonal antibody Nivolumab will be administered once prior to tumor resection. The second dose will be administered prior to TIL administration and dosing will continue every 4 weeks for up to 2 years.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
France	Centre Léon Berard	Lyon
Germany	Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen
Germany	Universitätsklinikum Schleswig-Holstein - Campus Lübeck	Lübeck	Schleswig-Holstein
Germany	Klinikum rechts der Isar der Technischen Universität München	München	Bavaria
Greece	Attikon University General Hospital	Athens	Attiki
Greece	Laiko General Hospital of Athens	Athens	Attiki
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	Barcelona
Spain	University Hospital Vall d'Hebron	Barcelona
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Regional Universitario de Malaga - Hospital General	Málaga
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Switzerland	Universitätsspital Basel	Basel
Switzerland	Universitaetsspital Bern	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Guy's Hospital	London	England
United Kingdom	The Royal Marsden NHS Foundation Trust	London	England
United States	University of Maryland	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	MD Anderson at Cooper	Camden	New Jersey
United States	University of Cincinnati	Cincinnati	Ohio
United States	Ohio State University	Columbus	Ohio
United States	University of Colorado	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	University of California, San Diego	La Jolla	California
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Morristown Medical Center	Morristown	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Huntsman Cancer Hospital	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Moffitt Cancer Center	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Iovance Biotherapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Greece,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	To evaluate the efficacy of autologous TIL in combination with CPIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as determined by objective response rate (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by Investigator	Up to 60 months
Primary	Safety Profile Measured by Grade =3 TEAEs	To characterize the safety profile of autologous TIL in combination with CPIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as measured by the incidence of Grade = 3 treatment-emergent adverse events (TEAEs)	Up to 60 months
Secondary	Complete Response Rate	To evaluate efficacy parameters such Complete Response (CR) rate per RECIST 1.1, as assessed by the Investigator	Up to 60 months
Secondary	Duration of Response	To evaluate efficacy parameters such Duration of Response (DOR) per RECIST 1.1, as assessed by the Investigator	Up to 60 months
Secondary	Disease Control Rate	To evaluate efficacy parameters such Disease Control Rate (DCR) per RECIST 1.1, as assessed by the Investigator	Up to 60 months
Secondary	Progression-Free Survival	To evaluate efficacy parameters such Progression-Free Survival (PFS) per RECIST 1.1, as assessed by the Investigator	Up to 60 months
Secondary	Overall Survival	To evaluate efficacy parameters such Overall Survival (OS)	Up to 60 months