Metastatic Melanoma, Squamous Cell Carcinoma of the Head and Neck, Non-small Cell Lung Cancer
Conditions
Keywords
LN-144, LN-145, Cell Therapy, Autologous Adoptive Cell Transfer, Autologous Adoptive Cell Therapy, Cellular Immuno-therapy, Tumor Infiltrating Lymphocytes, TIL, IL-2, Multiple Tumor Type, Lifileucel, Pembrolizumab, LN-145-S1, Ipilimumab, Nivolumab, ICI, Immune Checkpoint Inhibitor, Aldesleukin, Nivolumab-relatlimab, Platinum doublet chemotherapy agents, Cisplatin, Carboplatin, Paclitaxel, Nab-Paclitaxel, Non-small cell lung cancer, Melanoma
Brief summary
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.
Detailed description
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 (NMA) lymphodepletion regimen, followed by infusion of autologous TIL followed by the administration of aldesleukin. 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.
Interventions
BIOLOGICALLifileucel
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 aldesleukin administration. Lifileucel will be administered to patients once (on Day 0) during the study.
BIOLOGICALLN-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 aldesleukin administration. TIL will be administered to patients once (on Day 0) during the study.
DRUGPembrolizumab
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.
BIOLOGICALLN-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 aldesleukin administration. TIL will be administered to patients once (on Day 0) during the study.
DRUGIpilimumab
Monoclonal antibody Ipilimumab will be administered as a single dose prior to tumor resection.
DRUGNivolumab
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.
Nivolumab-relatlimab will be administered following tumor resection and will continue every 4 weeks thereafter for up to 2 years.
DRUGCisplatin
Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
DRUGCarboplatin
Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
DRUGPaclitaxel
Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
DRUGNab-Paclitaxel
Nab-Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
DRUGPemetrexed
Pemetrexed administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Optional continuation maintenance every 3 weeks, if applicable.
Sponsors
Iovance Biotherapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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). Stage IV NSCLC with no actionable mutations (EGFR, ALK, ROS1) with effective targeted therapy (Cohorts 3D and 3E). * Cohorts 1A, 1D, 2A, 3A, 3D and 3E: If previously treated, patients must have progressed on or after most recent therapy and must not have received ICIs 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). Patients in Cohort 1D may have had no prior therapy for advanced disease. Patients in Cohorts 3D and 3E may have had no prior systemic therapy for Stage IV disease. * 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 ICI (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 ICI 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, 1D, 2A, 3A, 3B, 3C, 3D and 3E. 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 aldesleukin, 4 months after their last dose of pembrolizumab, 5 months after their last dose of ipilimumab or nivolumab, or nivolumab-relatlimab; 6 months after the last dose of carboplatin; 14 months after the last dose of cisplatin; and 6 months after the last dose of pemetrexed, paclitaxel, or nab-paclitaxel, 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 or history of leptomeningeal 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, 1D, 2A, 3A, 3C, 3D and 3E 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 to be administered in the pertinent cohort(s). * Patients who have a left ventricular ejection fraction (LVEF) \< 45% or who are New York Heart Association Class II or higher. A cardiac stress test demonstrating any irreversible wall movement abnormality in any patients ≥60 years of age or in patients who have a history of ischemic heart disease, cardiac chest pain, or clinically significant atrial and/or ventricular arrhythmias. * 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. * Patients in Cohorts 1D, 3D, or 3E who previously received adjuvant or neoadjuvant ICI(s) for non-metastatic disease and had an immune-related AE(s) requiring systemic steroid treatment or discontinuation of immune checkpoint inhibitor therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 60 months | 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 |
| Safety Profile Measured by Grade ≥3 TEAEs | Up to 60 months | 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) |
| 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 | Up to 60 months | Feasibility is measured by the percentage of patients for whom lifileucel is successfully manufactured and meets release specification and defined as the number of patients with lifileucel product that meets specification divided by the total number of patients who had tumor resection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
Countries
Canada, France, Germany, Greece, Spain, Switzerland, United Kingdom, United States
Contacts
Primary ContactIovance Biotherapeutics Study Team
Outcome results
None listed