Clinical Trial 18309

Cancer Type:
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

  • Patients with unresectable or metastatic melanoma (Stage IIIc or Stage IV), who progressed following ≥1 line of prior systemic therapy, including immune checkpoint inhibitor (e.g., anti-PD-1), and if BRAF mutation-positive, after BRAF inhibitor systemic therapy
  • Must be ≥ 18 years and ≤ 70 years of age at the time of consent. Enrollment of patients > 65 years of age may be allowed after consultation with the Medical Monitor.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of ≥3 months.
  • In the opinion of the Investigator, must be able to complete all study-required procedures.
  • Patients of childbearing potential must be willing to practice an approved method of birth control during treatment and for 4 months after receiving all protocol related therapy.
  • Must have adequate hematologic parameters and organ function
  • Seronegative for the HIV antibody, hepatitis B antigen, and hepatitis C antibody or antigen.
  • Must have recovered from all prior therapy-related AEs to Grade 1 or less (per CTCAE v4.03), except for alopecia or vitiligo prior to enrollment (tumor resection)
  • 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 anti-PD-1/anti-PD-L1 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 that included a nonmyeloablative or myeloablative chemotherapy regimen (not applicable for patients in retreatment Cohort 3).
  • Patients with symptomatic and/or untreated brain metastases (of any size and any number). Patients with definitively treated brain metastases, who can be considered for enrollment after discussion with Medical Monitor, must be stable for 2-4 weeks prior to the start of treatment (nonmyeloablative lymphodepletion).
  • Pregnant or breastfeeding.
  • Patients who are on a systemic steroid therapy at a dose of > 10 mg of prednisone or equivalent per day.
  • Patients who have active medical illness(es) that in the opinion of the Investigator would pose increased risk for study participation, such as systemic infections requiring antibiotics, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system.
  • 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.
  • Patients who have obstructive or restrictive pulmonary disease and a documented FEV1 (forced expiratory volume in 1 second) of ≤ 60%.
  • Patients who have a left ventricular ejection fraction (LVEF) less than 45%.
  • Patients who have obstructive or restrictive pulmonary disease and a documented FEV1 (forced expiratory volume in 1 second) of ≤ 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).
  • Patients with known allergic reaction to antibiotics of aminoglycoside group (i.e., streptomycin, gentamicin).
  • Patients who have been shown to be BRAF mutation positive (V600), but have not received prior systemic therapy with a BRAF-directed kinase inhibitor.