Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer

Iovance Biotherapeutics

Status and phase

Enrolling

Phase 2

Conditions

Metastatic Non Small Cell Lung Cancer

Treatments

Biological: LN-145

Study type

Interventional

Funder types

Industry

Identifiers

NCT04614103

IOV-LUN-202

2024-510778-26-00

2020-003629-45 (EudraCT Number)

Details and patient eligibility

About

This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic non-small-cell lung cancer

Full description

LN-145 is a ready-to-infuse TIL therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI and further optimized by Iovance for the treatment of patients with metastatic NSCLC. The cell transfer therapy used in this study involves patients receiving a non-myeloablative (NMA) lymphodepleting preparative regimen, followed by infusion of autologous TIL, then finally followed by the administration of IL-2.

Enrollment

170 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients who are over 70 years of age may be allowed to enroll after discussion with the Medical Monitor.
Have historically or pathologically confirmed diagnosis of metastatic Stage IV NSCLC without EGFR, ALK, or ROS1 genomic alterations.
For patients who have actionable mutations (other than EGFR, ALK, or ROS1 genomic alterations), 1 additional line of therapy with the appropriate health authority approved targeted therapy is required.
Patients must have documented radiographic disease progression on or after the first-line therapy, including concurrent or sequential ICI and platinum-based chemotherapy ± bevacizumab. No more than 1 prior line is allowed if ICI and platinum-based chemotherapy were administered concurrently and no more than 2 prior lines are allowed for sequential administration of platinum-based chemotherapy and ICI as 2 separate lines.
LN-145 manufacture is allowed for patients who have residual resectable disease after completion of the platinum-based chemotherapy component of the front-line ICI and platinum-based chemotherapy combination and meet all eligibility criteria except documented disease progression. These patients must intend to receive TIL therapy after disease progression
Prior systemic therapy in the adjuvant or neoadjuvant setting, or as part of definitive chemoradiotherapy, will count as a line of therapy if the patient had disease progression during or within 12 months after the completion of such therapy.
At least 1 resectable lesion for TIL production and at least one remaining measurable lesion, as defined by RECIST v1.1
Have adequate organ function
LVEF > 45%, NYHA Class 1
Have adequate pulmonary function
ECOG performance status of 0 or 1
Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and up to 12 months after all protocol-related therapy

Exclusion criteria

Patients who have EGFR, ALK or ROS1 driver mutations
Patients who have symptomatic, untreated brain metastases.
Patients who have had allogeneic organ transplant or prior cell therapy within the past 20 years
Patients who have any form of primary immunodeficiency
Patients who are on systemic steroid therapy ≥ 10 mg/day of prednisone or equivalent.
Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment
Patients who have had another primary malignancy within the previous 3 years
Participation in another interventional clinical study within 21 days

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

170 participants in 5 patient groups

Cohort 1

Experimental group

Description:

Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) \< 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression

Treatment:

Biological: LN-145

Cohort 2

Experimental group

Description:

Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment

Treatment:

Biological: LN-145

Cohort 3

Experimental group

Description:

Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation

Treatment:

Biological: LN-145

Cohort 4

Experimental group

Description:

Patients, regardless of tumor PD-L1 expression status prior to ICI treatment, who have meet all inclusion/exclusion criteria except the requirement to have documented disease progression may elect to have the tumor harvest procedure and TIL production prior to disease progression on their current anticancer treatment. Documentation of progressive disease and identification of a target lesion for RECIST v1.1 assessment is required at Baseline for these patients.

Treatment:

Biological: LN-145

Retreatment Cohort

Experimental group

Description:

Patients who were previously treated with LN-145 in Cohort 1, 2, 3, or 4.

Treatment:

Biological: LN-145