Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) In Combo With Durvalumab in Non-Small Cell Lung Cancer

NCT ID: NCT03419559

Last Updated: 2019-04-16

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-28
• Study Completion Date: 2024-12-31

Brief Summary

This study is a Phase 2, open-label, multicenter study evaluating adoptive cell therapy (ACT) with autologous TIL therapy (LN-145) in combination with Anti-PD-L1 inhibitor durvalumab.

Detailed Description

LN-145 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI. The cell transfer therapy used in this study involves patients receiving a nonmyeloablative (NMA) lymphocyte depleting preparative regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2.

Conditions

Non Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LN-145 in combination with durvalumab

After nonmyeloablative (NMA) lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

Group Type: EXPERIMENTAL

LN-145

Intervention Type: BIOLOGICAL

adoptive cell therapy (ACT) with autologous TIL therapy

Durvalumab

Intervention Type: DRUG

PD-L1 antagonist monoclonal antibody

Interventions

LN-145

adoptive cell therapy (ACT) with autologous TIL therapy

Intervention Type: BIOLOGICAL

Durvalumab

PD-L1 antagonist monoclonal antibody

Intervention Type: DRUG

Other Intervention Names

TIL, autologous tumor infiltrating lymphocytes; MEDI4736

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of Stage III or Stage IV NSCLC and progressed after ≤ 3 lines of prior systemic therapy in the locally advanced or metastatic setting
• Have at least 1 lesion resectable for TIL generation
• Measurable disease as defined by RECIST v1.1
• Male or female, ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and estimated life expectancy of ≥ 3 months
• Adequate bone marrow function at screening
• Adequate organ function at screening
• A washout period from prior anticancer therapy(ies) of a minimum duration is required prior to first study treatment
• Recovered from all prior anticancer therapy-related AEs to Grade 1 or less (per CTCAE v4.03) prior to enrollment
• Female patients of childbearing potential and male patients with partners of childbearing potential patient must agree to use contraception while on study and during the timeframes as specified following the last dose of study drug(s) received, or until the first dose of the subsequent anticancer therapy, whichever is longer
• Evidence of postmenopausal status or negative urine or serum pregnancy test for female premenopausal patients

Exclusion Criteria

• History of other malignancies, except for the following: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, curatively-treated thyroid cancer, or other solid tumors curatively treated with no evidence of disease for ≥ 3 years
• Patients who have received prior cell therapy
• Patients who have received prior checkpoint inhibitors: such as anti-PD-1, anti-PD-L1 inhibitors, and durvalumab
• Active or prior documented autoimmune or inflammatory disorders
• History of primary or acquired immunodeficiency syndrome, history of allogeneic organ transplant that requires therapeutic immunosuppression
• Received live or attenuated vaccination within 28 days prior to the start of NMA-LD
• Patients with a history of hypersensitivity to any component of the study drugs
• Mean QT interval ≥ 470 msec
• Patients who have a left ventricular ejection fraction (LVEF) of < 45% or who are New York Heart Association (NYHA) Class 2 or higher
• Serious illnesses or medical conditions, which would pose increased risk for study participation and/or compliance with the protocol
• Patients who have obstructive or restrictive pulmonary disease and have a documented FEV1 (forced expiratory volume in 1 second) of ≤ 60%
• Active central nervous system metastases and/or leptomeningeal disease
• Female patients who are pregnant or breastfeeding
• Active infection including tuberculosis (TB), hepatitis B, hepatitis C, or HIV
• Current or prior use of immunosuppressive medication within 28 days before the first dose of study treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iovance Biotherapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Iovance Medical Monitor

Role: STUDY_DIRECTOR

Iovance Biotherapeutics, Inc.

Locations

University of California San Diego, Moores Cancer Center

La Jolla, California, United States

University of California, Los Angeles, Santa Monica Hematology/Oncology

Los Angeles, California, United States

University of Louisville James Graham Brown Cancer Center

Louisville, Kentucky, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Morristown Medical Center Atlantic Hematology Oncology

Morristown, New Jersey, United States

UPMC Cancer Center

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Washington Medical Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

IOV-LUN-201

Identifier Type: -

Identifier Source: org_study_id