Cancer individualized vaccine! Tlpldc has a strong therapeutic effect on stage IV melanoma, with a disease-free survival rate of 73% in 24 months!

February 8, 2020 / BIOON / -- Elios therapeutics is a biopharmaceutical company dedicated to developing innovative individual therapeutic cancer vaccine Recently, at the asco-sitc clinical immunooncology conference in 2020, the company announced the results of subgroup analysis of tlpldc (tumor lysate, particle loading, dendritic cells) vaccine in the phase IIB clinical trial of melanoma Tlpldc vaccine is a kind of individualized treatment method which uses patients' own blood and tumor cells Tumor samples are collected at the time of removal, frozen, and then sent to the laboratory, where they are used to make autogenous tumor lysates and loaded into yeast cell wall granules (ycwp) The binding was then introduced into the patient's dendritic cells to produce the final tlpldc vaccine It only takes about two weeks from tumor resection to vaccination The study was a prospective, randomized, double-blind, placebo-controlled phase IIB study conducted in patients with stage III (Advanced) and stage IV (metastatic) melanoma who had been removed to evaluate the efficacy and safety of tlpldc vaccine In these studies, 144 patients were randomized to receive tlpldc vaccine or placebo to prevent recurrence These patients were vaccinated within 3 months after the completion of standard care (SOC) treatment, respectively at 0, 1, 2, 6, 12, 18 months The protocol has been revised to allow the use of an approved checkpoint inhibitor for adjuvant (postoperative) treatment The primary end point of the study was disease-free survival (DFS) at 24 months, and the secondary end point included 36 months of DFS and total survival (OS), which was compared between the tlpldc vaccine group and the placebo group In view of the high rate of early recurrence in high-risk melanoma patients and the time required for vaccine to activate the immune system, the primary efficacy analysis was conducted for the intention to treat (ITT) population and the per treatment (PT) population in advance PT analysis included all patients who completed primary immunization with tlpldc or placebo vaccine series (PVS) for 6 months The main analysis data published before showed that in PT analysis, compared with placebo group, tlpldc treatment group had a significant improvement in disease-free survival rate at 24 months (62.9% vs 34.8%; HR = 0.52 [95% CI: 0.27-0.98], P < 0.041), indicating that the relative risk of disease recurrence was reduced by nearly 50% In the intention to treat (ITT) analysis, there was no significant improvement in disease-free survival at 24 months (38.5% vs 27%, P = 0.974) in the tlpldc treatment group and placebo group, but in this analysis, the trend of improvement in overall survival at 24 months (86.4% vs 75.1%, P = 0.15) was stronger The subgroup analysis published at the meeting evaluated the efficacy according to disease stage, immunotherapy and checkpoint inhibition PT analysis showed that in patients with stage IV melanoma, the 24-month disease-free survival rate of tlpldc vaccine group was significantly higher than that of placebo group (73.0% vs 0%, P = 0.002), indicating that the relative risk of disease recurrence in these patients was statistically significant and clinically significant ITT analysis also showed improvement (43.0% vs 0%, P = 0.098) Stage IV patients were more likely to receive checkpoint inhibitors (50% vs 26%, P = 0.003) At the 24-month evaluation time point, no DFS difference was observed between the tlpldc vaccine group and the placebo group in patients with stage III melanoma Compared with stage IV patients, stage III patients usually experience relapse after a longer period of time, so 36 month DFS evaluation will determine the therapeutic effect of dlpldc vaccine in stage III patients In addition, although the difference was not statistically significant due to the sample size, it was observed that patients treated with tlpldc vaccine combined with standard nursing checkpoint inhibitors had a clinically significant improvement in DFS at 24 months compared with patients treated with checkpoint inhibitors alone The results showed that tlpldc combined with checkpoint inhibitors had synergistic antitumor effect As mentioned before, tlpldc vaccine has good tolerance 31.7% of patients in placebo group and 35.9% of patients in tlpldc treatment group have related adverse events, most of which are level 1 or level 2 This study will continue to be carried out in accordance with the research protocol until the 36 month DFS and OS milestone end point, which is expected to be reached in June 2020 Mark B faries, MD, director of oncology surgery and co director of the melanoma project, Los Angeles Clinical Research Institute, said: "patients with stage III and stage IV melanoma who have completed the preliminary treatment have a high risk of disease recurrence, which represents a serious unmet medical demand In the challenging stage of stage IV disease, it is of great significance to achieve a disease-free survival rate of 73% Importantly, in these studies, we found that when tlpldc is combined with checkpoint inhibitors, there may be a synergistic antitumor response This approach may help to provide patient response and prevent disease recurrence " Tlpldc is an autotherapy cancer vaccine, which is made of patients' own cancer cells It aims to stimulate the immune system to recognize tumor cells and fight against specific (or unique) cancer of patients: (1) this immunotherapy can present tumor antigens in particles with pathogen related molecular characteristics (PAMPs); (2) the presenting pathogen carrying tumor antigens triggers both innate and adaptive This mechanism can overcome the inhibition of IL-10, reduce Treg and increase CD8 T cells in tumor Tlpldc (tumor lysate, particle loading, dendritic cells) vaccine is a unique immunotherapy, whether in the preparation method or in the delivery mode The vaccine is individualized, which means it's made from a patient's tumor and blood Each patient's tumor has a unique antigen characteristic different from other patients' tumor, and the dendritic cells (DC) found in the blood are the most effective antigen presenting cells in the body Once tlpldc is injected, it will transfer all tumor antigen pools of patients to the immune system, generate innate and adaptive double immune response, activate T cells, and trigger the immune system to recognize, search for and destroy any cells containing antigens and specific mutations derived from their tumors Historically, the development of autogenous cancer vaccine is quite arduous, and it usually takes several months from tumor biopsy to administration Elios has simplified the process, which takes about two weeks from tumor removal to vaccination This makes the individualized vaccine highly feasible and will eventually be convenient for community and academic oncologists to use in practice Buddy long, CEO of Elios therapeutics, said: "based on the encouraging data of this study and recent discussions with FDA on the end of phase II study, we are planning to conduct tlpldc vaccine registration study in patients with phase III and IV melanoma We will continue to focus on our mission to provide this safe and effective treatment for melanoma patients as soon as possible " Original source: Elios therapeutics presentations new phase IIB data for personalized cancer vaccine in high risk melanoma patients at the 2020 asco-sitc clinical immune oncology Symphony