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Clinical Trial 20270

Cancer Type: Immunotherapy
Study Type: Treatment
NCT#: NCT03645928

Phase: Phase II
Prinicipal Investigator: Benjamin Creelan

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Overview

Study Title

A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN-144 or LN-145) in Patients with Solid Tumors (IOV-COM-202)

Summary

LN-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.

Objective

Primary: -To evaluate the efficacy of autologous TIL LN-144/LN-145 in combination with pembrolizumab in MM, HNSCC< or NSCLC patients or TIL LN-145 as a single therapy in relapsed or refractory (r/r) NSCLC patients, who have previously progressed on or after treatment with CPIs, as determined by ORR, using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as assessed by Investigator -To characterize the safety profile of TIL LN-144/LN-145 in combination with pembrolizumab in MM, HNSCC, and NSCLC patients or TIL LN-145 as a single therapy in r/r NSCLC patients as measured by the incidence of Grade ≥3 treatment-emergent adverse events (TEAEs) Secondary: -To further evaluate the efficacy of autologous TIL LN-144/LN-145 in combination with pembrolizumab in MM, HNSCC, and NSCLC patients or TIL LN-145 as a single therapy in NSCLC patients using CR rate, duration of response (DOR), disease control rate (DCR), PFS using RECIST 1.1 as assessed by Investigator, and OR Exploratory: -To explore the persistence of TIL LN-144/LN-145 in combination with pembrolizumab or TIL LN-145 cells as a single therapy, and its resultant immune correlates that may affect response, outcome, and toxicity variables -To explore efficacy parameters (excluding OS) using the immune-related Response Evaluation Criteria in Solid Tumors (irRECIST), as assessed by Investigator -To assess respective, indication-specific, health-related quality-of-life (HRQoL) parameters

Treatments

Therapies

Medications

IL-2 (Interleukin-2); MESNA (); Pembrolizumab (Keytruda); TIL (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

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: If previously treated, Participants 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. Participants 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: MM Participants must have previously received systemic therapy with a PD-1 blocking antibody. NSCLC Participants must have previously received systemic therapy with any CPI (except for those Participants with known oncogene drivers (eg, EGFR, ALK, ROS) who have mutations that are sensitive to targeted therapies) as part of 1 - 3 prior lines of therapy.
  • 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. Participants must be ≥ 12 years at the time of consent for Cohort 1B. Enrollment of Participants > 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
  • Participants 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

  • Participants with melanoma of uveal/ocular origin.
  • Participants who have received an organ allograft or prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen within the past 20 years.
  • Participants with symptomatic and/or untreated brain metastases
  • Participants who are on systemic steroid therapy ≥ 10 mg/day of prednisone or other steroid equivalent. Participants receiving steroids as replacement therapy for adrenocortical insufficiency at ≤ 10 mg/day of prednisone or other steroid equivalent may be eligible.
  • Participants who are pregnant or breastfeeding.
  • Participants who have an active medical illness(es), which in the opinion of the Investigator, would pose increased risks for study participation
  • Cohort 1A, 2A and 3A Participants may not have a medical history of autoimmune disorders requiring treatment or active management.
  • Participants who have received a live or attenuated vaccination within 28 days prior to the start of treatment
  • Participants who have any form of primary immunodeficiency
  • Participants with a history of hypersensitivity to any component of the study drugs
  • Participants who have a left ventricular ejection fraction (LVEF) > 45% or who are New York Heart Association Class II or higher
  • Participants not meeting the pulmonary function requirements as stated: Participants 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
  • Participants 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.

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