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

Sponsor

Iovance Biotherapeutics, Inc. (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT03419559

Collaborator

(none)

Enrollment

Locations

Arm

81.1

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Feb 28, 2018

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LN-145 in combination with durvalumab After nonmyeloablative (NMA) lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.	Biological: LN-145 adoptive cell therapy (ACT) with autologous TIL therapy Other Names: TIL, autologous tumor infiltrating lymphocytes Drug: Durvalumab PD-L1 antagonist monoclonal antibody Other Names: MEDI4736

Arm

Intervention/Treatment

Experimental: LN-145 in combination with durvalumab

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

Biological: LN-145

adoptive cell therapy (ACT) with autologous TIL therapy

Other Names:

TIL, autologous tumor infiltrating lymphocytes

Drug: Durvalumab

PD-L1 antagonist monoclonal antibody

Other Names:

MEDI4736

Outcome Measures

Primary Outcome Measures

Objective Response Rate [A maximum of 24 months]
To evaluate efficacy using the objective response rate (ORR)
≥ Grade 3 Treatment-Emergent Adverse Event [A maximum of 24 months]
To evaluate the safety as measured by any ≥ Grade 3 treatment-emergent adverse event (TEAE) rate

Secondary Outcome Measures

Duration of Response [A maximum of 24 months]
To further evaluate efficacy such as the duration of response (DOR)
Progression Free Survival [A maximum of 24 months]
To further evaluate efficacy such as progression free survival (PFS)
Overall Survival [A minimum of 5 years]
To further evaluate efficacy such as overall survival (OS)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego, Moores Cancer Center	La Jolla	California	United States	92093
2	University of California, Los Angeles, Santa Monica Hematology/Oncology	Los Angeles	California	United States	90095
3	University of Louisville James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
4	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
5	Morristown Medical Center Atlantic Hematology Oncology	Morristown	New Jersey	United States	07960
6	UPMC Cancer Center	Pittsburgh	Pennsylvania	United States	15232
7	Vanderbilt University	Nashville	Tennessee	United States	37232
8	University of Washington Medical Center	Seattle	Washington	United States	98195-0001