A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors
Brief SummaryA 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 pembrolizumab or TIL LN-145/LN-145-S1 as a single therapy.
Detailed DescriptionLN-144 (Lifileucel)/LN-145/LN-145-S1 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process for the treatment of patients with advanced unresectable or metastatic melanoma, advanced squamous cell carcinoma of the head and neck, and 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, Cohort 2A, and Cohort 3A will receive TIL plus pembrolizumab. Patients in Cohorts 1B and Cohort 3B will receive TIL as a single therapy.
Inclusion and Exclusion Criteria
- Inclusion Criteria
- Must have a confirmed diagnosis of malignancy of their receptive histologies: unresectable or metastatic melanoma Stage IIIC or Stage IV (Cohorts 1A and 1B), advanced recurrent or metastatic squamous cell carcinoma of the head and neck (Cohort 2A), or Stage III or Stage IV non-small cell lung cancer (Cohorts 3A and 3B).
- Cohorts 1A, 2A, and 3A only: Patients must be CPI naive. 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. Cohorts 1A, 2A, and 3A may have received up to 3 prior systemic anticancer therapies
- Cohorts 1B and 3B: Patients must have previously received systemic therapy with PD-1 blocking antibody for MM or any CPI for NSCLC as part of ≤ 3 prior lines of therapy. Patients must have radiologically documented disease progression while receiving or after the completion of the most recent prior treatment.
- Must have at least 1 resectable lesion
- Must have a remaining measurable disease as defined by RECIST 1.1 following tumor resection
- Must be ≥18 years at the time of consent for Cohorts 1A, 2A, 3A, and 3B. 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 receiving all protocol-related therapy. Exclusion Criteria
- Patients with melanoma of uveal/ocular origin.
- Patients who have received an organ allograft or prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen within the past 20 years.
- Patients with symptomatic and/or 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
- Patients may not have active or prior documented autoimmune or inflammatory disorders
- 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
- Pulmonary function requirement
- Patients having any of the following require pulmonary function testing (PFT) with post-bronchodilator values of forced expiratory volume (FEV1)/forced vital capacity (FVC) > 0.7 and FEV1 > 50%: History of cigarette smoking of ≥ 20 pack-years and still smoking, ceased smoking within the past 2 years, history of chronic obstructive pulmonary disease (COPD), any signs or symptoms of respiratory dysfunction
- Patients who have had another primary malignancy within the previous 3 years
- Participation in another interventional clinical study within 21 days of the initiation of treatment.
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.