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

Sponsor

Iovance Biotherapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04614103

Collaborator

(none)

Enrollment

Locations

Arms

66.8

Anticipated Duration (Months)

2.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Metastatic Non Small Cell Lung Cancer	Biological: LN-145 Biological: LN-145	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

95 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 7, 2021

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 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 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. Other Names: TIL, Autologous Tumor Infiltrating Lymphocytes
Experimental: Cohort 2 Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment	Biological: LN-145 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. Other Names: TIL, Autologous Tumor Infiltrating Lymphocytes
Experimental: Cohort 3 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 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. Other Names: TIL, Autologous Tumor Infiltrating Lymphocytes
Experimental: Retreatment Cohort Patients who were previously treated with LN-145 in Cohort 1, 2, or 3.	Biological: LN-145 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. Other Names: TIL, Autologous Tumor Infiltrating Lymphocytes

Outcome Measures

Primary Outcome Measures

Objective Response Rate [Up to 60 months]
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 Cohort 3 and the Retreatment Cohort

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 targeted therapy will be allowed.
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	UC San Diego Moores Cancer Center	La Jolla	California	United States	92037
3	Christiana Care Health System	Newark	Delaware	United States	19713
4	University of Florida Health Cancer Center	Gainesville	Florida	United States	32610
5	Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
6	AdventHealth Cancer Institute	Orlando	Florida	United States	32804
7	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
8	Augusta University	Augusta	Georgia	United States	30912
9	Rush University Medical Center	Chicago	Illinois	United States	60612
10	University of Illinois Hospital & Health Sciences System	Chicago	Illinois	United States	60612
11	University of Louisville	Louisville	Kentucky	United States	40202
12	University of Maryland	Baltimore	Maryland	United States	21201
13	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
14	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
15	Henry Ford Health System	Detroit	Michigan	United States	48202
16	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
17	MD Anderson Cooper	Camden	New Jersey	United States	08103
18	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
19	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
20	University of Rochester Medical Center	Rochester	New York	United States	14642
21	University of North Carolina	Chapel Hill	North Carolina	United States	27514
22	Novant Health - Charlotte	Charlotte	North Carolina	United States	28204
23	Novant Health - Winston-Salem	Winston-Salem	North Carolina	United States	27103
24	Atrium Health Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
25	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45219
26	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
27	University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
28	Oregon Health and Science University	Portland	Oregon	United States	97239
29	Allegheny General Hospital	Natrona Heights	Pennsylvania	United States	15065
30	Avera Medical Group Cancer Institute	Sioux Falls	South Dakota	United States	57105
31	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
32	Baptist Cancer Center	Memphis	Tennessee	United States	38120
33	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
34	VCU Medical Center (Virginia Commonwealth University)	Richmond	Virginia	United States	23298
35	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
36	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2C1
37	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montréal		Canada	QC H2X 3E4
38	Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam		Netherlands	1066