Elios Therapeutics announced positive top-line results from a Phase IIb clinical trial evaluating its lead immuno-oncology candidate, the TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine, in patients with Stage III and IV resected melanoma. The study met its primary endpoint by demonstrating a statistically significant reduction in the risk of disease recurrence at 24-months (disease-free survival; DFS) in the per treatment (PT) population.
The phase IIb prospective, randomized, double-blind, placebo-controlled trial was designed to evaluate the safety and efficacy of the TLPLDC vaccine in 144 patients with resected Stage III and IV melanoma. The patients were randomized to receive either the vaccine or placebo to prevent recurrence. TLPLDC or placebo vaccines were initiated within three months of completion of standard of care (SoC) therapies and were given at 0, 1, 2, 6, 12, and 18 months. Patients were followed for recurrence per SoC. The primary efficacy analysis was performed on the intent-to-treat (ITT) and the per treatment (PT) populations as co-primary analyses given the high early recurrence rate often seen in patients with advanced melanoma.
For all 144 patients enrolled in the study (ITT), including those who were never, or incompletely vaccinated, the recurrence rate was 66% in the placebo arm compared to 54% in the vaccine arm, representing an 18% clinically meaningful, though statistically non-significant, reduction in the relative risk of disease recurrence. However, the PT analysis of all patients who completed the primary vaccine series (six-months) of TLPLDC or placebo, demonstrated a 56% recurrence rate in the placebo arm versus 29% in the vaccine arm, representing a highly statistically significant 50 percent reduction in the relative risk of disease recurrence. In addition, an initial assessment of 36-month follow-up data on all patients indicates that the TLPLDC vaccine benefit is not only durable but continues to show benefit beyond 24-months. No safety concerns were identified, with only one-third of patients experiencing a related adverse event (AE), the majority of which were grade 1 or 2. As a result of this data, the data safety monitoring board for the trial recommended that the study continue as designed to the 36-month landmark endpoints of DFS and overall survival, anticipated in June 2020.
Melanoma develops in the cells (melanocytes) that produce melanin—the pigment that gives skin its color. Melanoma can also form in eyes and, rarely, in internal organs, such as intestines. The exact cause of all melanomas isn’t clear, but exposure to ultraviolet (UV) radiation from sunlight or tanning lamps and beds increases the risk of developing melanoma. Stage III and IV melanoma is considered advanced. In Stage III, the cancer cells have spread to nearby lymph nodes, but not to distant organs. In Stage IV melanoma (also known as metastatic melanoma), cancer cells have spread beyond the skin and regional lymph nodes to distant organs such as the liver, lungs or brain, or distant lymph nodes and areas of the skin.
About the TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine
The TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine is a unique type of immunotherapy, both in how it is made and how it is delivered. The vaccine is personalized, meaning it is made from a patient’s tumor and blood. Every patient’s tumor has a unique antigenic profile unlike any other and dendritic cells found in the blood are the most potent antigen presenting cells in the body. Once TLPLDC is administered, it delivers the patient’s complete repertoire of tumor antigens to the immune system, creating a dual innate and adaptive immune response, activating fighter T-cells, and triggering the immune system to recognize, and seek out and destroy any cells containing the antigens and specific mutations from their tumor.