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

Abstract

Background: Checkpoint inhibitors (CPI) in combination with cell-based vaccines may produce synergistic antitumor immunity. The primary analysis of the randomized and blinded phase IIb trial in resected stage III/IV melanoma demonstrated TLPLDC is safe and improved 24-month disease-free survival (DFS) in the per treatment (PT) analysis. Here, we examine efficacy within pre-specified and exploratory subgroups.

Methods: Stage III/IV patients rendered disease-free by surgery were randomized 2:1 to TLPLDC vaccine versus placebo. The pre-specified PT analysis included only patients completing the primary vaccine/placebo series at 6 months. Kaplan-Meier analysis was used to compare 24-month DFS among subgroups.

Results: There were no clinicopathologic differences between subgroups except stage IV patients were more likely to receive CPI. In stage IV patients, 24-month DFS was 43% for vaccine versus 0% for placebo (p = 0.098) in the ITT analysis and 73% versus 0% (p = 0.002) in the PT analysis. There was no significant difference in 24-month DFS when stratified by use of immunotherapy or CPI. For patients with resected recurrent disease, 24-month DFS was 88.9% versus 33.3% (p = 0.013) in the PT analysis. All benefit from vaccination was in the PT analysis; no benefit was found in patients receiving up to three doses.

Conclusion: The TLPLDC vaccine improved DFS in patients completing the primary vaccine series, particularly in the resected stage IV patients. The efficacy of the TLPLDC vaccine will be confirmed in a phase III study evaluating adjuvant TLPLDC + CPI versus Placebo + CPI in resected stage IV melanoma patients.

Keywords: cancer vaccine; immunotherapy; melanoma; personalized medicine.

FIGURE 1

Kaplan‐Meier curves demonstrating 24‐month DFS stratified by stage for the ITT analysis (1A, left) and PT analysis (1B, right). Log rank p‐values are displayed within each figure

FIGURE 2

Kaplan‐Meier curves demonstrating 24‐month DFS in the PT analysis. Each arm is grouped by treatment arm (TLPLDC vs. placebo) and whether the patient received immunotherapy (IO) (yes/no, left) or checkpoint inhibitor (yes/no, right)

FIGURE 3

Kaplan‐Meier curves demonstrating 24‐month DFS stratified by Disease‐Free Interval, characterized as Recurrent or Primary disease, where Primary disease included patients without prior melanoma and those with a disease‐free interval of less than 3 months. Recurrent disease included patients with DFI >3 months

FIGURE 4

Kaplan‐Meier curves demonstrating 24‐month DFS comparing TLPLDC vs. placebo for patients receiving ≥1 dose (A) top left, ≥2 doses (B) top right, ≥3 doses (C) bottom left, and ≥4 doses (D) bottom right