Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors

Iovance Biotherapeutics

Status and phase: Enrolling; Phase 2

Conditions: Squamous Cell Carcinoma of the Head and Neck; Non-small Cell Lung Cancer; Metastatic Melanoma

Treatments: Drug: Nivolumab; Drug: Pembrolizumab; Biological: Lifileucel; Biological: LN-145; Biological: LN-145-S1; Drug: Ipilimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03645928

2018-001608-12 (EudraCT Number)

IOV-COM-202

Details and patient eligibility

About

A prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL LN-144 (Lifileucel)/LN-145 in combination with checkpoint inhibitors or TIL LN-144 (Lifileucel)/LN-145/LN-145-S1 as a single agent therapy.

Full description

LN-144 (Lifileucel)/LN-145/LN-145-S1 is an adoptive cell transfer therapy that utilizes an autologous TIL for the treatment of patients with unresectable or metastatic melanoma, advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, and locally advanced or metastatic non-small cell lung cancer. The adoptive cell transfer therapy used in this study involves patients receiving a nonmyeloablative (NMA) lymphodepletion regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2. Patients in Cohorts 1A, 2A, 3A and 3C will receive TIL plus checkpoint inhibitors. Patients in Cohorts 1B, 1C, and 3B will receive autologous TIL as a single therapy.

Enrollment: 178 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Must have a confirmed diagnosis of malignancy of their receptive histologies: unresectable or metastatic melanoma Stage IIIC to IV (Cohorts 1A,1B and 1C), advanced, recurrent or metastatic HNSCC (Cohort 2A), or Stage III or Stage IV non-small cell lung cancer (Cohorts 3A, 3B, and 3C).
• Cohorts 1A, 2A, and 3A: If previously treated, patients must have progressed on or after most recent therapy and must not have received CPIs as part of one of the counted lines of prior therapy. Patients must have radiologically documented disease progression while receiving or after the completion of the most recent prior treatment. Patients may have received up to 3 prior systemic anticancer therapies (except for Cohort 3A, where patients whose tumors harbor actionable mutations may have received up to 4 prior systemic therapies)
• Cohorts 1B, 1C, 3B, and 3C: Unresectable or metastatic melanoma patients in Cohorts 1B or 1C must have previously received systemic therapy with a PD-1 blocking antibody. NSCLC patients in Cohort 3B must have previously received systemic therapy with any CPI (except for those patients with known oncogene driver mutations that are sensitive to targeted therapies) as part of 1 - 3 prior lines of therapy. NSCLC patients in Cohort 3C must have previously received 1 line of CPI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neoadjuvant settings are allowed.
• Must have at least 1 resectable lesion
• Must have remaining measurable disease as defined by RECIST 1.1 following tumor resection
• Must be ≥ 18 years at the time of consent for Cohorts 1A, 1C, 2A, 3A, 3B, and 3C. Patients must be ≥ 12 years at the time of consent for Cohort 1B. Enrollment of patients > 70 years of age may be allowed after consultation with the Medical Monitor.
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and an estimated life expectancy of ≥ 6 months.
• Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of birth control during treatment and for 12 months after their last dose of IL-2, 4 months after their last dose of pembrolizumab, or 5 months after their last dose of ipilimumab or nivolumab, whichever occurs later.

Exclusion Criteria

• Patients with melanoma of uveal/ocular origin.
• Patients who have a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years. Patients being retreated with TIL, as part of this study are not excluded.
• Patients who have symptomatic, untreated brain metastases
• Patients who are on systemic steroid therapy > 10 mg/day of prednisone or other steroid equivalent. Patients receiving steroids as replacement therapy for adrenocortical insufficiency at ≤ 10 mg/day of prednisone or other steroid equivalent may be eligible.
• Patients who are pregnant or breastfeeding.
• Patients who have an active medical illness(es), which in the opinion of the Investigator, would pose increased risks for study participation
• Cohort 1A, 2A, 3A, and 3C patients may not have a medical history of autoimmune disorders (including pneumonitis) requiring treatment or active management.
• Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment
• Patients who have any form of primary immunodeficiency
• Patients with a history of hypersensitivity to any component of the study drugs
• Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association Class II or higher
• Patients with respiratory dysfunction or history of smoking are excluded if not meeting either of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.7 or FEV1 > 50%.
• Patients who have had another primary malignancy within the previous 3 years
• Participation in another interventional clinical study within 21 days prior to the initiation of treatment.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

178 participants in 7 patient groups

Cohort 1A

Experimental group

Description:

LN-144 therapy in combination with pembrolizumab in patients with Stage IIIC to IV unresectable or metastatic melanoma with ≤ 3 prior lines of systemic therapy, excluding checkpoint inhibitors (CPI).

Treatment:

Biological: Lifileucel

Drug: Pembrolizumab

Cohort 1B

Experimental group

Description:

LN-145-S1 therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is proto-oncogene B-Raf (BRAF) V600 mutation positive, patients must have received a BRAF inhibitor with or without a mitogen-activated extracellular signal-related kinase (MEK) inhibitor.

Treatment:

Biological: LN-145-S1

Cohort 1C

Experimental group

Description:

LN-144 Generation 3 (Gen 3) therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is BRAF V600 mutation positive, patients must have received BRAF inhibitor with or without a MEK inhibitor.

Treatment:

Biological: Lifileucel

Cohort 2A

Experimental group

Description:

LN-145 therapy in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding CPIs.

Treatment:

Biological: LN-145

Drug: Pembrolizumab

Cohort 3A

Experimental group

Description:

LN-145 therapy in combination with pembrolizumab in patients with locally advanced or metastatic (Stage III or Stage IV) non-small-cell lung cancer (NSCLC) with ≤ 3 prior lines of systemic therapy, excluding CPIs, or ≤ 4 lines if 2 or more of the lines are TKI therapy for those with tumors that harbored actionable mutations (eg, EGFR, ALK, ROS).

Treatment:

Biological: LN-145

Drug: Pembrolizumab

Cohort 3B

Experimental group

Description:

LN-145 therapy as a single agent in patients with Stage III or Stage IV NSCLC, who have previously received 1-3 lines of prior systemic therapy. Patients with known oncogene drivers (eg, EGFR, ALK, ROS) who have mutations that are sensitive to targeted therapies are not required to have received prior systemic therapy with CPIs.

Treatment:

Biological: LN-145

Cohort 3C

Experimental group

Description:

LN-145 therapy in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who have previously received 1 line of CPI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neo-adjuvant settings are allowed.

Treatment:

Drug: Ipilimumab

Biological: LN-145

Drug: Nivolumab