Phase III multicenter trial of eltrapuldencel-T: Autologous dendritic cells loaded with irradiated autologous tumor cells (DC-TC) in granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with metastatic melanoma (INTUS trial).
ABSTRACT
Background: Melanomas harbor non-synonymous mutations that can result in unique, immunogenic tumor associated antigens (TAA). Recognition of TAA can be induced or enhanced by vaccination. The best source of TAA for this purpose may be proliferating, self-renewing, autologous tumor cells (patient-specific tumor stem cells). Patients with stage IV and recurrent stage III melanoma were treated with repeated s.c. injections of autologous dendritic cells loaded with antigens from irradiated tumor cells derived from autologous melanoma cell lines (DC-TC), and suspended in GM-CSF. In a single arm Phase II trial (n = 54) 5-year survival was 50%. In a randomized Phase II trial (n = 42), 2-year survival was 72% for DC-TC vs. 31% for control patients (HR = 0.27, p = 0.007). Toxicities associated with DC-TC were minimal (n = 72). Improvements in manufacturing have increased the probability of establishing a tumor cell line and decreased the time needed to manufacture DC-TC. Eltrapuldencel-T (DC-TC) was granted special protocol assessment (SPA) and fast track designation by the U.S. Food and Drug Administration in association with approval of this pivotal trial.
Methods: INTUS is a Phase III, double-blind, randomized, placebo-controlled trial. Eligible patients have stage IV or recurrent stage III melanoma with at least one lesion amenable to surgical resection. Resected tumor is transferred to a manufacturing facility to grow the cell line. After successful establishment of a cell line and referral for treatment, 250 patients with good performance status (ECOG 0-1) will be stratified by whether they have no evidence of disease, non-measurable disease by RECIST, or measureable disease with elevated LDH or without elevated LDH, then randomized 2:1 to receive either DC-TC or autologous mononuclear cells. Patients undergo leukapheresis to obtain mononuclear cells for each arm. Both products are suspended in 500 micrograms of GM-CSF and injected weekly for 3 weeks, and then monthly for 5 months. The endpoint is overall survival (death from any cause) [NCT01875653]. Clinical trial information: NCT01875653