A prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL \[LN-144/LN-145 (lifileucel)\] in combination with immune checkpoint inhibitors or TIL \[LN-144/LN-145 (lifileucel) and LN-145-S1\] as a single agent therapy.
TIL \[LN-144/LN-145 (lifileucel) and LN-145-S1\] 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 lymphodepletion (NMA-LD) regimen, followed by autologous TIL infusion , then aldesleukin administration. Patients in Cohorts 1A, 1D, 2A, 3A, 3C, 3D, and 3E will receive TIL plus immune checkpoint inhibitors. Patients in Cohorts 1B, 1C, and 3B will receive autologous TIL as a single therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
225
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor-infiltrating lymphocytes (TIL). After NMA-LD, patients receive lifileucel, followed by aldesleukin administration. Lifileucel will be administered to patients once (on Day 0) during the study.
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 aldesleukin administration. TIL will be administered to patients once (on Day 0) during the study.
Humanized antibody. Pembrolizumab will be administered after tumor resection and will continue every 3 weeks or every 6 weeks for up to 2 years.
Objective Response Rate
To evaluate the efficacy of autologous TIL in combination with ICIs 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
Time frame: Up to 60 months
Safety Profile Measured by Grade ≥3 TEAEs
To characterize the safety profile of autologous TIL in combination with ICIs 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)
Time frame: Up to 60 months
Percentage of patients for whom lifileucel is successfully manufactured and meets release specification
To evaluate the feasibility of producing lifileucel using tumor samples obtained before (Cohort 3D) or during (Cohort 3E) frontline platinum doublet chemotherapy and pembrolizumab in patients with Stage IV NSCLC
Time frame: Up to 60 months
Complete Response Rate
To evaluate efficacy using Complete Response (CR) rate per RECIST 1.1, as assessed by the Investigator
Time frame: Up to 60 months
Duration of Response
To evaluate efficacy using Duration of Response (DOR) per RECIST 1.1, as assessed by the Investigator
Time frame: Up to 60 months
Disease Control Rate
To evaluate efficacy using Disease Control Rate (DCR) per RECIST 1.1, as assessed by the Investigator
Time frame: Up to 60 months
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A tumor sample is resected from each patient and cultured ex vivo to expand the population of TIL, then TIL with high levels of PD-1 surface expression are selected. After NMA-LD, patients receive their autologous PD-1-selected TIL (LN-145-S1), followed by aldesleukin administration. TIL will be administered to patients once (on Day 0) during the study.
Monoclonal antibody Ipilimumab will be administered as a single dose prior to tumor resection.
Monoclonal antibody. Nivolumab will be administered once prior to tumor resection. The second dose will be administered prior to starting NMA-LD and will continue every 4 weeks for up to 2 years.
Monoclonal antibody (nivolumab) and monoclonal antibody (relatlimab). Nivolumab-relatlimab will be administered after tumor resection and will continue every 4 weeks for up to 2 years.
Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
Nab-Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
Pemetrexed administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Optional continuation maintenance every 3 weeks, if applicable.
University of California, San Diego
La Jolla, California, United States
University of Southern California
Los Angeles, California, United States
University of California, Los Angeles
Los Angeles, California, United States
University of Colorado
Denver, Colorado, United States
Yale University
New Haven, Connecticut, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
University of Louisville
Louisville, Kentucky, United States
University of Maryland
Baltimore, Maryland, United States
...and 24 more locations
Progression-Free Survival
To evaluate efficacy using Progression-Free Survival (PFS) per RECIST 1.1, as assessed by the Investigator
Time frame: Up to 60 months
Overall Survival
To evaluate efficacy using Overall Survival (OS)
Time frame: Up to 60 months