Clinical trial NCT03419559: Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) In Combo With Durvalumab in Non-Small Cell Lung Cancer
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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: LN-145
Cell Therapy
Autologous Adoptive Cell Transfer
Cellular Immuno-therapy
TIL
IL-2
Durvalumab
Lead sponsor: Iovance Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate
timeFrame: A maximum of 24 months
measure: ≥ Grade 3 Treatment-Emergent Adverse Event
timeFrame: A maximum of 24 months
Secondary outcomes:
measure: Duration of Response
timeFrame: A maximum of 24 months
measure: Progression Free Survival
timeFrame: A maximum of 24 months
measure: Overall Survival
timeFrame: A minimum of 5 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego, Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles, Santa Monica Hematology/Oncology
state: California
city: Louisville
country: United States
facility: University of Louisville James Graham Brown Cancer Center
state: Kentucky
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Morristown
country: United States
facility: Morristown Medical Center Atlantic Hematology Oncology
state: New Jersey
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Iovance Biotherapeutics, Inc.
name: Iovance Medical Monitor
role: STUDY_DIRECTOR
References: