Safety And Efficacy Of Autologous Tumor Lysate Particle Loaded Dendritic Cell (Tlpldc) Vaccination In Combination With Systemic Therapies In Patients With Metastatic Melanoma

Background: The treatment of melanoma has changed drastically with the advent of immunotherapy, particularly checkpoint inhibition (CPI). Unfortunately, only 50-60% of tumors respond to current immunotherapy. The autologous tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine utilizes the whole antigenic panel of the patient9s tumor to stimulate T-cells and may work synergistically with other immunotherapies. We have previously demonstrated both safety and efficacy of TLPLDC vaccine as adjuvant therapy for patients (pts) with resected stage III or IV melanoma who complete the primary vaccine series. Here, we describe results in pts with metastatic melanoma treated with the TLPLDC vaccine together with other approved therapies. Methods: The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles which are then phagocytosed by autologous dendritic cells ex-vivo. Pts who recurred while enrolled in a randomized phase IIb trial of adjuvant TLPLDC vaccine (crossover arm) and pts with metastatic melanoma with measurable disease (MM arm) were offered TLPLDC vaccine in an open-label fashion in addition to other approved therapies as determined by their treating physician. The vaccine is given via intradermal injection monthly x4 followed by boosters at six and nine months. Tumor response is measured by RECIST 1.1 criteria. Results: To date, 53 pts have been enrolled (28 in the crossover arm and 25 in the MM arm). Within the crossover arm, 18 pts had received TLPLDC as part of the phase IIb trial, 8 were from the placebo group, and 2 patients withdrew prior to vaccination. Within the MM arm, 2 were excluded for no evidence of disease at time of vaccination and 1 withdrew. The vaccine was well tolerated, with 24% of patients experiencing a treatment-related adverse event (AE), with no grade ≥3 AE. Concurrent therapies were varied in the crossover arm, but 36% received CPI, compared with 68% in the MM arm. Of those receiving CPI, 59% had \u003e1 immune-related AE, none of which were grade ≥3. In the crossover arm, 12-month overall survival (OS) was 83.3% in the vaccine-naive cohort at median follow-up of 6.0 months vs. 94.7% in the re-vaccinated cohort at median follow-up of 9.0 months (p=0.961). In the MM arm, 12-month OS was 61.2% at a median follow-up of 7.7 months. In a pooled analysis of 33 evaluable pts, vaccine-naive pts (n=21) had a 42.9% non-progression rate compared to a 66.7% non-progression rate in re-vaccinated pts (n=12). Conclusion: Vaccination with the TLPLDC vaccine in combination with approved systemic therapies in MM pts is well tolerated, with acceptable rates of immune-related AE when combined with CPI. Additionally, vaccination, and specifically re-vaccination, may provide clinical benefit particularly if used in combination with other approved therapies. Citation Format: Robert Connor Chick, Annelies T. Hickerson, Guy Travis Clifton, Phillip M. Kemp Bohan, Tommy A. Brown, Jessica L. Cindass, John W. Myers, Timothy J. Vreeland, Doreen O. Jackson, Diane F. Hale, Kaitlin M. Peace, Garth S. Herbert, Xianzhong Yu, Thomas Wagner, George E. Peoples. Safety and efficacy of autologous tumor lysate particle loaded dendritic cell (TLPLDC) vaccination in combination with systemic therapies in patients with metastatic melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6536.