Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors

Phase 2

Recruiting

• Conditions: Squamous Cell Carcinoma of the Head and Neck; Metastatic Melanoma; Non-small Cell Lung Cancer
• Interventions: Biological: LN-145; Biological: Lifileucel; Biological: LN-145-S1; Drug: Pembrolizumab; Drug: Ipilimumab; Drug: Nivolumab

• Registration Number: NCT03645928
• Lead Sponsor: Iovance Biotherapeutics, Inc.

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2018-08-22
• Study First Submitted QC: 2018-08-22
• Study First Posted: 2018-08-24
• Study Start: 2019-05-07
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-04
• Last Update Posted: 2024-04-08
• Primary Completion: 2029-08-09
• Study Completion: 2029-08-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 178

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1A	Pembrolizumab	LN-144 therapy in combination with pembrolizumab in patients with Stage IIIC to IV unresectable or metastatic melanoma with ≤ 3 prior lines of systemic therapy, excluding checkpoint inhibitors (CPI).
Cohort 2A	LN-145	LN-145 therapy in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding CPIs.
Cohort 3A	Pembrolizumab	LN-145 therapy in combination with pembrolizumab in patients with locally advanced or metastatic (Stage III or Stage IV) non-small-cell lung cancer (NSCLC) with ≤ 3 prior lines of systemic therapy, excluding CPIs, or ≤ 4 lines if 2 or more of the lines are TKI therapy for those with tumors that harbored actionable mutations (eg, EGFR, ALK, ROS).
Cohort 1A	Lifileucel	LN-144 therapy in combination with pembrolizumab in patients with Stage IIIC to IV unresectable or metastatic melanoma with ≤ 3 prior lines of systemic therapy, excluding checkpoint inhibitors (CPI).
Cohort 1B	LN-145-S1	LN-145-S1 therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is proto-oncogene B-Raf (BRAF) V600 mutation positive, patients must have received a BRAF inhibitor with or without a mitogen-activated extracellular signal-related kinase (MEK) inhibitor.
Cohort 1C	Lifileucel	LN-144 Generation 3 (Gen 3) therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is BRAF V600 mutation positive, patients must have received BRAF inhibitor with or without a MEK inhibitor.
Cohort 2A	Pembrolizumab	LN-145 therapy in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding CPIs.
Cohort 3A	LN-145	LN-145 therapy in combination with pembrolizumab in patients with locally advanced or metastatic (Stage III or Stage IV) non-small-cell lung cancer (NSCLC) with ≤ 3 prior lines of systemic therapy, excluding CPIs, or ≤ 4 lines if 2 or more of the lines are TKI therapy for those with tumors that harbored actionable mutations (eg, EGFR, ALK, ROS).
Cohort 3B	LN-145	LN-145 therapy as a single agent in patients with Stage III or Stage IV NSCLC, who have previously received 1-3 lines of prior systemic therapy. Patients with known oncogene drivers (eg, EGFR, ALK, ROS) who have mutations that are sensitive to targeted therapies are not required to have received prior systemic therapy with CPIs.
Cohort 3C	LN-145	LN-145 therapy in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who 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 neo-adjuvant settings are allowed.
Cohort 3C	Nivolumab	LN-145 therapy in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who 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 neo-adjuvant settings are allowed.
Cohort 3C	Ipilimumab	LN-145 therapy in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who 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 neo-adjuvant settings are allowed.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	Up to 60 months	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
Safety Profile Measured by Grade ≥3 TEAEs	Up to 60 months	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)

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival	Up to 60 months	To evaluate efficacy parameters such Progression-Free Survival (PFS) per RECIST 1.1, as assessed by the Investigator
Overall Survival	Up to 60 months	To evaluate efficacy parameters such Overall Survival (OS)
Complete Response Rate	Up to 60 months	To evaluate efficacy parameters such Complete Response (CR) rate per RECIST 1.1, as assessed by the Investigator
Duration of Response	Up to 60 months	To evaluate efficacy parameters such Duration of Response (DOR) per RECIST 1.1, as assessed by the Investigator
Disease Control Rate	Up to 60 months	To evaluate efficacy parameters such Disease Control Rate (DCR) per RECIST 1.1, as assessed by the Investigator

Trial Locations

Locations (45)

University of Colorado; 🇺🇸 Denver, Colorado, United States

The Royal Marsden NHS Foundation Trust; 🇬🇧 London, England, United Kingdom

University of Southern California; 🇺🇸 Los Angeles, California, United States

Universitätsklinikum Schleswig-Holstein - Campus Lübeck; 🇩🇪 Lübeck, Schleswig-Holstein, Germany

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Huntsman Cancer Hospital; 🇺🇸 Salt Lake City, Utah, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Mount Sinai Medical Center; 🇺🇸 Miami Beach, Florida, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Centre Léon Berard; 🇫🇷 Lyon, France

University Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

University of California, San Diego; 🇺🇸 La Jolla, California, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Columbia University; 🇺🇸 New York, New York, United States

MD Anderson at Cooper; 🇺🇸 Camden, New Jersey, United States

Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States

Universitätsklinikum Carl Gustav Carus; 🇩🇪 Dresden, Sachsen, Germany

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Attikon University General Hospital; 🇬🇷 Athens, Attiki, Greece

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

ICO l'Hospitalet - Hospital Duran i Reynals; 🇪🇸 Barcelona, Spain

Bristol Haematology and Oncology Centre; 🇬🇧 Bristol, United Kingdom

Universitaetsspital Bern; 🇨🇭 Bern, Switzerland

Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

Hospital Regional Universitario de Malaga - Hospital General; 🇪🇸 Málaga, Spain

Georgetown University Medical Center; 🇺🇸 Washington, District of Columbia, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland

Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States

Laiko General Hospital of Athens; 🇬🇷 Athens, Attiki, Greece

Universitätsspital Basel; 🇨🇭 Basel, Switzerland

Klinikum rechts der Isar der Technischen Universität München; 🇩🇪 München, Bavaria, Germany

Orlando Health Cancer Institute; 🇺🇸 Orlando, Florida, United States

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Guy's Hospital; 🇬🇧 London, England, United Kingdom