Article Text

Download PDFPDF

300 Final analysis of a prospective, randomized, double-blind, placebo-controlled phase IIb trial of tumor lysate, particle-loaded, dendritic cell vaccine in stage III/IV melanoma: 36-month analysis
  1. Lexy Adams1,
  2. Robert Chick1,
  3. Guy Clifton1,
  4. Timothy Vreeland1,
  5. Patrick McCarthy1,
  6. Anne O’Shea1,
  7. Phil Kemp Bohan1,
  8. Annelies Hickeron1,
  9. John Myers1,
  10. Jessica Cindass1,
  11. Diane Hale1,
  12. Mark Faries2,
  13. John Hyngstrom3,
  14. Adam Berger4,
  15. James Jakub5,
  16. Jeffrey Sussman6,
  17. Montaser Shaheen7,
  18. Thomas Wagner8 and
  19. George Peoples9
  1. 1Brooke Army Medical Center, San Antonio, TX, USA
  2. 2John Wayne Cancer Institute, Los Angeles, CA, USA
  3. 3University of Utah, Salt Lake City, UT, USA
  4. 4Rutgers Cancer Institute of New Jersey, philadelphia, PA, USA
  5. 5Mayo Clinic, Rochester, MN, USA
  6. 6University of Cincinatti, Cincinnati, OH, USA
  7. 7University of Arizona, Pheonix, AZ, USA
  8. 8Orbis Health Solutions, Greenville, SC, USA
  9. 9Cancer Vaccine Development Program, San Antonio, TX, USA


Background The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is created ex vivo by loading autologous dendritic cells (DC) with yeast cell wall particles (YCWP) containing autologous tumor lysate, thus delivering tumor antigens to the DC cytoplasm via phagocytosis. TLPLDC then activates a robust T cell response against the unique antigens for each patient. The primary analysis of the prospective, randomized, multi-center, double-blind, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma showed TLPLDC improved 24-month disease-free survival (DFS) in the per-treatment (PT) analysis (patients completing the 6-month primary vaccine series). Here, we examine the secondary endpoint of 36-month DFS and overall survival (OS).

Methods Patients with resected stage III/IV melanoma were randomized 2:1 to TLPLDC vaccine or placebo (autologous DC loaded with empty YCWP). Treatments were given at 0, 1, 2, 6, 12 and 18 months. The protocol was amended to include patients receiving concurrent checkpoint inhibitors (CPIs) to follow changes in standard of care. The co-primary endpoints were 24-month DFS by intention-to-treat (IT) analysis and per-treatment (PT) analysis, with secondary endpoints including 36-month DFS and OS by ITT and PT analysis, pre-specified analysis by stage, and safety as measured by CTCAE v4.03.

Results Overall, 103 patients received TLPLDC and 41 placebo. In PT analysis, 65 patients received TLPLDC and 32 placebo. Total adverse events (AEs), grade 3+ AEs, and serious AEs (SAEs) were similar in placebo vs TLPLDC groups, with one related SAE per treatment arm. By ITT analysis, 36-month OS was 76.2% for TLPLDC vs 70.3% for placebo (HR 0.72, p=0.437) and 36-month DFS was 35.6% vs 27.1% (HR 0.95, p=0.841). By PT analysis, 36-month DFS was improved with TLPLDC (57.5% vs 35.0%; HR 0.50, p=0.025, figure 1). This effect was even more dramatic in resected stage IV patients (36-month DFS: 60.9% vs 0%; HR 0.12, p=0.001, figure 2).

Conclusions This phase IIb trial again demonstrates the safety of the TLPLDC vaccine, and an improved 36-month DFS in patients with resected stage III/IV melanoma who complete the primary vaccine series, particularly in the stage IV subgroup. Next, a phase III trial will evaluate the efficacy of TLPLDC vaccine as adjuvant treatment for resected stage IV melanoma, with patients randomized to receive standard of care PD-1 inhibitors + TLPLDC versus PD-1 inhibitors + placebo.

Abstract 300 Figure 1

36-month disease free survival for patients receiving TLPLDC vs placebo by PT analysis

Abstract 300 Figure 2

36-month disease free survival for subset of stage IV melanoma patients receiving TLPLDC vs placebo by PT analysis

Trial Registration This is a phase IIb clinical trial registered under NCT02301611

Ethics Approval This study was approved by Western IRB, protocol 20141932.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.