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

NCT03419559 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: IOV-LUN-201
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 8

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.

Conditions

Non Small Cell Lung Cancer

Keywords

LN-145; Cell Therapy; Autologous Adoptive Cell Transfer; Cellular Immuno-therapy; TIL; IL-2; Durvalumab

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate

  To evaluate efficacy using the objective response rate (ORR)

  A maximum of 24 months

• ≥ Grade 3 Treatment-Emergent Adverse Event

  To evaluate the safety as measured by any ≥ Grade 3 treatment-emergent adverse event (TEAE) rate

  A maximum of 24 months

Secondary Outcomes (3)

• Duration of Response

  A maximum of 24 months

• Progression Free Survival

  A maximum of 24 months

• Overall Survival

  A minimum of 5 years

Study Arms (1)

LN-145 in combination with durvalumab

EXPERIMENTAL

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

Biological: LN-145; Drug: Durvalumab

Interventions

LN-145 BIOLOGICAL

adoptive cell therapy (ACT) with autologous TIL therapy

Also known as: TIL, autologous tumor infiltrating lymphocytes

LN-145 in combination with durvalumab

Durvalumab DRUG

PD-L1 antagonist monoclonal antibody

Also known as: MEDI4736

LN-145 in combination with durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Iovance Biotherapeutics, Inc.: lead

Study Sites (8)

University of California San Diego, Moores Cancer Center

La Jolla, California, 92093, United States

Location

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

Los Angeles, California, 90095, United States

Location

University of Louisville James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Morristown Medical Center Atlantic Hematology Oncology

Morristown, New Jersey, 07960, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195-0001, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Toll-Like Receptor 1; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Toll-Like Receptors; Receptors, Pattern Recognition; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Iovance Medical Monitor

  Iovance Biotherapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2018
• First Posted: February 5, 2018
• Study Start: February 28, 2018
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2024
• Last Updated: April 16, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)