A novel, personalized therapeutic cancer vaccine continues to show promise for patients with Stage III or IV melanoma at high risk for recurrence following complete surgical resection. Vaccine developer Elios Therapeutics has publicized Phase 2b clinical trials results for the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine, showing that one version of the vaccine resulted in a statistically significant improvement in 36-month disease-free survival (DFS), compared to placebo or an alternative version of the vaccine.
A Closer Look
The “personalized” TLPLDC vaccine is made from a patient’s tumor and blood. Based on the observation that each patient’s tumor has a unique antigenic profile, Elios developed its vaccine platform to harness dendritic cells with the goal to deliver the patient’s complete set of tumor antigens to the immune system. Theoretically, this exposure will initiate a dual innate and adaptive immune response, activating T cells, and triggering the immune system to recognize, seek out, and destroy cells containing the antigens and specific mutations from the target tumor.
Making the TLPLDC vaccine takes approximately three weeks from resection to injection.
The vaccine platform is being investigated as monotherapy and in combination with standard-of-care checkpoint inhibitor therapies for the treatment of late-stage melanoma. Recently announced Phase 2b data analysis includes 144 participants who were randomized to receive one of two versions of the vaccine or placebo. Version A was produced by isolating dendritic cells (DCs) from 120mL of blood; Version B was developed with DCs isolated after a single injection of filgrastim followed by harvesting of 50-70mL of blood. Filgrastim is used to increase white blood cell and DC counts.
Treatment with vaccine B resulted in clinical outcomes similar to placebo. Compared to vaccine B and placebo, vaccine A resulted in a statistically significant improvement in 36-month DFS (51.8 vs. 23.4 vs 27.1 percent, respectively; p=0.027) and OS (92.9 vs. 62.8 vs 70.3 percent, respectively; p=0.022) in the ITT population. DFS improvement with vaccine A was seen across both Stage III (49.7 vs. 29.4 percent; p=0.066) and IV (68.6 vs. 9.4 percent; p=0.0582) patients.
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 percent; p=0.039).
Treatment with the vaccine was well-tolerated. While just over one-third of patients experienced a treatment-related adverse event, more than >90 percent of these were rated as grades 1 or 2.
A Promising Development
The notion of a melanoma vaccine is not new, and multiple types of vaccines are in various stages of development and testing. The TLPLDC vaccine could prove to be a valuable weapon in the fight against melanoma. If the vaccine is shown effective in Phase 3 trials and garners FDA approval, the three-week individual vaccine development process may be beneficial for patients with late-stage disease, with or without the use of add-on melanoma therapies.
The TLPLDC Vaccine
- Samples are collected at resection and frozen.
- Samples sent to the lab and used to create autologous tumor lysate, which is loaded into yeast cell wall particles (YCWP).
- This combination is introduced to the patient’s dendritic cells, leading to the creation of the final TLPLDC vaccine.
- Time from resection to injection of the vaccine is approximately three weeks.