Elios Therapeutics announced final data from a prospective, randomized, double-blind, placebo-controlled Phase IIb clinical trial evaluating adjuvant use of its personalized tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in patients with Stage III or Stage IV melanoma at high risk of recurrence following complete surgical resection.
"We now have long-term data demonstrating that use of the TLPLDC vaccine for the adjuvant treatment of high-risk melanoma correlates with a 93 percent increase in patients alive at three years without their disease returning. This trial also significantly improves our understanding of the optimal method of vaccine production," said Buddy Long, chief executive officer of Elios Therapeutics. "These new data, combined with the doubled rate of disease-free survival among patients treated with the vaccine and standard of care checkpoint inhibitors, further strengthen our confidence that the personalized TLPLDC vaccine provides a clinically meaningful benefit for people with high-risk melanoma. We look forward to advancing this vaccine with a registrational Phase III trial that will move us one step closer to bringing this important treatment to patients as soon as possible."
The TLPLDC vaccine is a personalized treatment that is created using a patient's own blood and tumor cells. Samples are collected at resection, frozen, and sent to the lab where they are used to create autologous tumor lysate, which is loaded into yeast cell wall particles. This combination is then introduced to the patient's dendritic cells, leading to the creation of the final TLPLDC vaccine. The time from resection to injection of the vaccine takes approximately three weeks.
The vaccine has been studied in a large randomized Phase IIb trial, and the newly reported data is from the pre-specified 36-month disease-free survival (DFS) and overall survival (OS) assessment by vaccine formulation, stage, and checkpoint inhibition. The analysis included all randomized patients in an intent-to-treat (ITT) analysis. Two versions of the vaccine, one produced by isolating dendritic cells (DCs) from 120 mL of blood (vaccine-A) and one with DCs isolated after a single injection of filgrastim followed by 50-70 mL of blood (vaccine-B), were tested in 144 participants who were randomized to receive either version of the vaccine or placebo to prevent recurrence.
A key finding showed that treatment with vaccine-B resulted in clinical outcomes similar to placebo. Producing the vaccine with filgrastim was intended to increase white blood cell and dendritic cell counts, requiring less blood to be drawn from patients to create the vaccine. While the use of filgrastim increased DC production, it takes only 72-hours to create the vaccine which was not enough time for the DCs to mature, rendering vaccine-B ineffective.
Importantly, vaccine-A, when compared to vaccine-B and placebo, resulted in a statistically significant improvement in 36-month DFS (51.8% vs. 23.4% vs 27.1%, respectively; p=0.027) and OS (92.9% vs. 62.8% vs 70.3%, respectively; p=0.022) in the ITT population.
Furthermore, the DFS improvement with vaccine-A was seen across both Stage III (49.7% vs. 29.4%; p=0.066) and IV (68.6% vs. 9.4%; p=0.0582) patients. Importantly, the addition of vaccine-A to current standard of care checkpoint inhibitors led to a statistically significant increase in 36-month DFS in the ITT population compared to treatment with checkpoint inhibitors alone (48.5% vs. 24.1%; p=0.039). As previously reported, treatment with the vaccine was well-tolerated with 34.7 percent of patients experiencing a treatment-related adverse event, and >90% being grades 1 or 2.
"To demonstrate a long-term survival benefit with low toxicity in a therapeutic is what we hope for in every clinical trial. Achieving this with an aggressive disease like melanoma offers great promise for patients," said Mark B. Faries, M.D., co-director of the Melanoma Program and head of Surgical Oncology at Cedars-Sinai at The Angeles Clinic and Research Institute, and principal investigator of the study. "With data showing a two-fold increase in disease-free survival with the vaccine alone and ...
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