Clinical Trial 18309

Cancer Type: Cutaneous
Interventions:Aldesleukin (Interleukin-2); IL-2 (Interleukin-2); Interleukin-2; Proleukin (Interleukin-2); TIL

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Amod Sarnaik

Overview

Study Title

A Phase 2, Multicenter, Single-arm Study to Assess the Safety, Feasibility, and Efficacy of Cell Transfer Therapy Using Autologous Tumor Infiltrating Lymphocytes (LN-144) Followed by IL-2 for Treatment of Metastatic Melanoma

Summary

The purpose of this study is to find out if an investigational product called LN-144 is safe to give to patients with metastatic melanoma and if processing tumors to obtain cells in a central lab works. LN-144 is also called "tumor infiltrating lymphocytes" (TIL).

Objective

Primary Objectives: To assess the safety and toxicities associated with the treatment regimen. To assess the feasibility of TIL production, defined as the percentage of patients with tumor resected from which LN-144 is successfully produced (manufacture of more than 1.5 billion viable cells). Secondary Objectives: To assess the feasibility of LN-144 administration followed by IL-2 (defined as the percentage of patients with tumor resected with LN-144 subsequently infused). To evaluate the anti-tumor activity defined by best overall response rate by RECIST 1.1 in patients who receive LN-144 followed by IL-2. Exploratory Objectives: To evaluate additional measures of efficacy for up to 24 months, including: progression-free survival (PFS), overall survival (OS), duration of response, and time to response. To explore potential immune correlates of response, outcome, and toxicity of the treatment.

Inclusion Criteria

  • Have measurable metastatic melanoma and at least one lesion that is resectable for TIL generation. The lesion must be of at least 1.5 cm in diameter and can be surgically removed with minimal morbidity (defined as any operation for which expected hospitalization is less than or equal to 3 days).
  • Have undergone at least one prior systemic treatment for metastatic melanoma.
  • Have either progressive disease or no response (i.e., no PR or CR) while receiving or after completion of most recent prior treatment.
  • Greater than 18 years of age at the time of consent. Patients greater than 65 years of age may be allowed in the study after discussion between the Principle Investigator and Medical Monitor.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • In the opinion of the Investigator, must be capable of participating and completing study procedures.
  • Patients of child bearing age or potential must be willing to practice birth control during treatment and for 4 months after receiving all protocol related therapy.
  • Must have a serum absolute neutrophil count (ANC) greater than 1000/mm^3, hemoglobin greater than 9.0 g/dL, and platelet count greater than 100,000/mm^3.
  • Have a serum ALT/SGPT and AST/SGOT less than 3 times the upper limit of normal (50 mL/min), and a total bilirubin less than or equal to 2 mg/dL (≤ 2 mg/dL). Patients with Gilbert's Syndrome must have a total bilirubin less than 3 mg/dL (> Seronegative for the HIV antibody, hepatitis B antigen, and hepatitis C antibody or antigen.
  • Must be EBV viral capsid antigen (VCA) IgG positive and/or, Epstein Barr nuclear antigen (EBNA) IgG positive, and have no clinical evidence of active EBV infection.
  • Must not have received systemic chemotherapy or immune therapy for 2 weeks (targeted therapy) and 4 weeks (all other anti-cancer therapy) at the time of enrollment, and there must be no intention of receiving any non-protocol systemic anti-cancer chemotherapy or immune therapy during the trial period.
  • Potential participants with documented Grade 2 or greater diarrhea or colitis as a result of previous treatment with ipilimumab, tremelimumab, anti-PD1 or anti-PD-L1 antibodies must have been asymptomatic for at least 6 months or had a normal colonoscopy post treatment, with uninflamed mucosa by visual assessment.
  • Have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an informed consent form (ICF) approved by an institutional review board (IRB), and agree to abide by the study restrictions and return to the site for the required assessments.

  • Exclusion Criteria

  • Patients with melanoma of uveal/ocular origin
  • Have received prior cell transfer therapy which included a non-myeloablative or myeloablative chemotherapy regimen.
  • Have more than 3 brain metastases. Note: Patients with one or two untreated or inadequately treated brain lesions or three or more adequately treated brain metastases may be eligible. If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been definitively treated and stable for one month. Brain metastases with significant edema or hemorrhage and metastases larger than 2 cm are excluded.
  • Pregnant or breastfeeding.
  • Are on a systemic steroid therapy regimen defined as the need for chronic steroid use for at least 7 or more days at a dose of greater than 10 mg of prednisone or equivalent per day.
  • Have active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced in the medical history by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  • Have any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
  • A history of severe immediate hypersensitivity reaction to IL-2, fludarabine, cyclophosphamide.
  • History of coronary revascularization or ischemic symptoms.
  • Estimated glomerular filtration rate (eGFR) less than 40 mL/min using the Cockcroft-Gault formula at Screening or have end-stage renal disorder requiring hemodialysis.
  • Left ventricular ejection fraction (LVEF) less than 45%. (Older patients [60 - 70 years], must have received an echocardiogram within the previous 60 days demonstrating LVEF ≥ 45%).
  • Have a documented forced expiratory volume in one second (FEV1) of less than or equal to 60%.
  • Have had another primary malignancy within the previous 3 years (with the exception of carcinoma in situ of the breast, urothelial cancer in situ, and non-melanoma skin cancer that has been adequately treated).