TLPLDC Personalized Cancer Vaccine
TLPLDC (tumor lysate, particle-loaded, dendritic cell) is an autologous therapeutic cancer vaccine that is made from a patient’s own cells and is designed to stimulate the immune system to recognize tumor cells and fight the patient's specific (or unique) cancer.
Elios Therapeutics's TLPLDC 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, says the company.
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.
Historically, autologous cancer vaccines have been rather onerous to develop, sometimes taking months between the tumor biopsy and administration. Elios has simplified the process so the time from resection to injection is approximately two weeks. This makes the vaccine highly feasible and will ultimately be easy for community and academic oncologists to adopt into their practices, says the company
A key finding of a recent clinical trial 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 the 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.
Elios Therapeutics, LLC, a wholly-owned subsidiary of Perseus Holdings, LLC., is a biopharmaceutical company developing a portfolio of innovative personalized therapeutic cancer vaccines targeting unmet medical needs across a broad range of tumor types.
TLPLDC Personalized Cancer Vaccine Indication
TLPLDC is indicated to prevent the reoccurrence of melanoma and achieve disease-free survival (DFS). Melanoma is more likely to grow and spread than other types of skin cancer. When diagnosed and treated at an early stage, melanoma has a high cure rate, however, patients with later stages of the disease carry a high risk for melanoma recurrence because some melanoma cells can remain in the body, even after surgery.
Skin cancer is the most common of all cancers. However, melanoma accounts for only about 1 percent of skin cancers, but causes a large majority of skin cancer deaths, says Cancer.org.
TLPLDC Personalized Cancer Vaccine Dosage
The TLPLDC vaccine is currently being studied as a monotherapy and in combination with standard-of-care checkpoint inhibitor therapies in a Phase IIb clinical trial for the treatment of late-stage melanoma at leading academic cancer centers in the USA. TLPLDC vaccine candidate is injected intradermally monthly x 3 followed by boosters at 6, 12, and 18 months.
TLPLDC Personalized Cancer Vaccine News
August 5, 2020 - 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 ~ 96 Percent of High-Risk Melanoma Patients Were Alive Three Years After Completing the Vaccine Series Compared to 77 Percent of those Treated with Placebo.
February 7, 2020 - A multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: A subgroup analysis presentation.
November 22, 2019 - Elios Therapeutics announced the initial assessment of 36-month follow-up data on all patients in this study indicated that the ‘TLPLDC vaccine benefit is not only durable but continues to increase beyond 24-months.’
July 17, 2019 - Elios Therapeutics, announced positive top-line results from the Company’s prospective, randomized, double-blind, placebo-controlled 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.
TLPLDC Personalized Cancer Vaccine Clinical Trials
Clinical Trial NCT02301611: Phase IIB TL + YCWP + DC in Melanoma
- This Phase IIb study is a prospective, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of the TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine in patients with resected Stage III and IV melanoma. The primary endpoint of the trial is two-year disease-free survival (DFS), and the secondary endpoint is three-year DFS and overall survival (OS).
In the study, 144 participants were randomized to receive either the vaccine or placebo to prevent a 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. The protocol was amended to allow concurrent checkpoint inhibitor therapy once approved for the adjuvant setting. Study participants 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. Secondary endpoints include 36-month DFS and overall survival (OS) which will be compared between the vaccinated and control groups as well as by vaccine formulation.
Clinical Trial NCT02678741: Multi-center Phase I/IIa Trial of an Autologous Tumor Lysate (TL) + Yeast Cell Wall Particles (YCWP) + Dendritic Cells (DC) Vaccine in Addition to Standard of Care Checkpoint Inhibitor of Choice in Metastatic Melanoma Patients With Measurable Disease - Last Update Posted: March 26, 2020.