Background: The autologous tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine has been shown to be safe and immunogenic while producing objective tumor responses in a variety of metastatic patients (pts). Here, we present the pre-specified interim results of a randomized, double blind phase IIb trial (NCT02301611) assessing the TLPLDC vaccine to prevent recurrences in high risk melanoma pts.
Methods: Stage III & IV resectable melanoma pts were identified prior to definitive surgery and consented for tumor collection. Pts were re-consented for treatment and randomized 2:1 (vaccine (V): placebo (P)). TLPLDC or placebo vaccines were initiated within 3 mos of completion of standard of care (SoC) therapies. Intradermal inoculations were given at 0, 1, 2, 6, 12, and 18 mos. Pts were followed for recurrence per SoC, and the primary endpoint is 2 yr disease-free survival (DFS). The interim was pre-specified at 6 mos from the 120th randomization. Survival analysis was performed on the intention-to-treat (ITT) and per treatment (PT) populations. The latter excludes early recurrences during the primary vaccine series (PVS) (up to 6 mos).
Results: The trial randomized 120 patients (V = 83, P = 37). There were no clinicopathologic or treatment-related differences between the groups except for median age (V = 65 yrs, P = 57 yrs, p = 0.02). There were 3:1 stage III:IV in both groups. Study-wide, only 33% of pts experienced treatment-related adverse events (AEs) with 98.6% being grade 1-2. There were no serious AEs or immune-mediated AEs. In the ITT analysis, there was no difference in recurrence (V = 56.6%, P = 54.1%, p = 0.65) at a median f/u of 11.9 mos. In the PT analysis (V = 51, P = 30), there was a trend toward decreased recurrences in the TLPLDC arm (V = 29.4%, P = 43.3%, p = 0.07) at a median f/u of 12.6 mos.
Conclusions: The TLPLDC vaccine is safe with minimal toxicity. Among pts completing the PVS period (6 mos), there is a strong trend toward fewer recurrences in the TLPLDC arm. This benefit will be confirmed at the primary analysis of 2 yr DFS; however, these early data provide an encouraging signal that a phase III trial for efficacy may be warranted. Clinical trial information: NCT02301611