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

Non Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 2 Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-145) In Combination With Anti-PD-L1 Inhibitor Durvalumab (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03419559
• Other study ID #: IOV-LUN-201
• Status: Withdrawn
• Phase: Phase 2
• Start date: February 28, 2018
• Est. completion date: December 2024

Study information

• Verified date: April 2019
• Source: Iovance Biotherapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2024
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Biological:
• LN-145
adoptive cell therapy (ACT) with autologous TIL therapy

Drug:
• Durvalumab
PD-L1 antagonist monoclonal antibody

Locations

Country	Name	City	State
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	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	Morristown Medical Center Atlantic Hematology Oncology	Morristown	New Jersey
United States	Vanderbilt University	Nashville	Tennessee
United States	UPMC Cancer Center	Pittsburgh	Pennsylvania
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Iovance Biotherapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	To evaluate efficacy using the objective response rate (ORR)	A maximum of 24 months
Primary	= 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	Duration of Response	To further evaluate efficacy such as the duration of response (DOR)	A maximum of 24 months
Secondary	Progression Free Survival	To further evaluate efficacy such as progression free survival (PFS)	A maximum of 24 months
Secondary	Overall Survival	To further evaluate efficacy such as overall survival (OS)	A minimum of 5 years