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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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A Phase 2 Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (TIL or LN-145) in Patients With Metastatic Non-Small-Cell Lung Cancer

Conditions
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Metastatic Non Small Cell Lung Cancer

Intervention / Treatment
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* Biological: LN-145
* Biological: LN-145


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are over 70 years of age may be allowed to enroll after consultation with the Medical Monitor. Have historically or pathologically confirmed diagnosis of metastatic Stage IV NSCLC without EGFR, ALK, or ROS genomic alterations. For patients who have actionable mutations (other than EGFR, ALK, or ROS 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 ROS 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) < 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression | Biological: LN-145<br>* 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.<br>* Other names: TIL, Autologous Tumor Infiltrating Lymphocytes;|
| Experimental: Cohort 2<br>Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment | Biological: LN-145<br>* 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.<br>* Other names: TIL, Autologous Tumor Infiltrating Lymphocytes;|
| Experimental: Cohort 3<br>Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation | Biological: LN-145<br>* 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.<br>* Other names: TIL, Autologous Tumor Infiltrating Lymphocytes;|
| Experimental: Cohort 4<br>Patients, regardless of tumor PD-L1 expression status prior to ICI treatment, who have meet all inclusion/exclusion criteria except the requirement to have documented disease progression may elect to have the tumor harvest procedure and TIL production prior to disease progression on their current anticancer treatment. Documentation of progressive disease and identification of a target lesion for RECIST v1.1 assessment is required at Baseline for these patients. | Biological: LN-145<br>* 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.<br>* Other names: TIL, Autologous Tumor Infiltrating Lymphocytes;|
| Experimental: Retreatment Cohort<br>Patients who were previously treated with LN-145 in Cohort 1, 2, 3, or 4. | Biological: LN-145<br>* 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.<br>* Other names: TIL, Autologous Tumor Infiltrating Lymphocytes;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LN-145, Cell Therapy, Autologous Adoptive Cell Therapy, Cellular Immuno-therapy, Tumor Infiltrating Lymphocytes, TIL, IL-2, Non Small Cell Lung Cancer, NSCLC, Second line Lung Cancer, Bronchial Neoplasms, Carcinoma, Lung Disease, Metastatic Lung Cancer, Metastatic Non Small Cell Lung Cancer, Metastatic NSCLC, Lung Carcinoma, PD-L1, Stage IV Lung Cancer, Stage IV Non-Small Cell Lung Cancer, Stage IV NSCLC, Systemic Therapy, 2nd line therapy, Second line therapy, CPI, Immune checkpoint inhibitor (ICI), NSCLC Recurrent, Recurrent Lung Cancer, Recurrent Lung Carcinoma