The final data of a personalized tumor lysate, particle-loaded, dendritic cell vaccine demonstrated that patients with stage III or IV melanoma with high-risk of recurrence after complete surgical resection had better survival benefit and disease-free survival rate with the vaccine over placebo, according to a press release from Elios Therapeutics.
The final data of a personalized tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine demonstrated that patients with stage III or IV melanoma with high-risk of recurrence after complete surgical resection had better survival benefit and disease-free survival (DFS) rate with the vaccine over placebo, according to a press release from Elios Therapeutics.
In the prospective, randomized, double-blind, placebo-controlled phase 2b clinical trial (NCT02301611), investigators observed a 92.9% survival rate at 3 years for patients in the intent-to-treat (ITT) population who completed the vaccine series versus 70.3% for those received placebo. There were 51.8% of patients who were disease-free at 3 years compared with 27.1%, respectively.
"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," Mark B. Faries, MD, 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, said in a statement. "With data showing a 2-fold increase in DFS with the vaccine alone and in combination with checkpoint inhibitors, we hope to one day change the narrative for people with melanoma—turning this disease into a chronic condition that can be treated and managed over time."
For the 144 patients included on the trial, there were 2 versions of the vaccine they could receive, and others were randomized to receive placebo. The first, vaccine-A, was produced by isolating dendritic cells from 120 mL of blood; the second, vaccine-B, was made using dendritic cells isolated after 1 injection of filgrastim followed by 50 mL to 70 mL of blood.
Compared with vaccine-B and placebo, vaccine-A showed a significantly improved 36-month DFS of 51.8% versus 23.4% with vaccine-B versus 27.1% with placebo in the ITT population (P =.027). The 36-month overall survival rate with these 3 agents was 92.9%, 62.8%, and 70.3%, respectively (P =.022).
When vaccine-A was added to the current standard of care checkpoint inhibitors, there was a statistically significant increase in DFS at 36 months for the ITT patients at 48.5% compared with checkpoint inhibitors alone at 24.1% (P =.039).
There were 34.7% of patients who experienced treatment-related adverse events, and over 90% of those were grade 1 or 2, showing that this treatment is well-tolerated.
To make the personalized treatment investigated in this study, investigators used the patient’s own blood and tumor cells by collecting samples at their resection, which are then frozen and sent to a lab. These samples are used to create autologous tumor lysate, loaded into yeast cell wall particles, and naturally taken up to the patient’s dendritic cells. There is about 3 weeks between resection of the samples to the injection of the vaccine and TLPLDC are injected intradermally every month for 3 months, after which patients receive boosters at 6, 12, and 18 months.
The data showed that vaccine-B had similar results to the placebo because there was not enough time for the dendritic cells to mature. Because vaccine-B used filgrastim, the time to create the vaccine took 72-hours. This method was used to increase patient’s white cell and dendritic cell counts and would require less blood to be drawn to make the vaccine.
"This trial significantly improves our understanding of the optimal method of vaccine production," Buddy Long, chief executive officer of Elios Therapeutics, said in a press release. "These new data, combined with the doubled rate of DFS 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 3 trial that will move us one step closer to bringing this important treatment to patients as soon as possible."
Elios Therapeutics Personalized Cancer Vaccine Demonstrates Long-Term Survival Benefit Among High-Risk Melanoma Patients in Phase IIb Final Analysis. News release. Elios Therapeutics. August 5, 2020. Accessed August 6, 2020. https://yhoo.it/2DI3fcQ