A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis

Abstract

Background: Melanoma therapy has changed dramatically over the last decade with improvements in immunotherapy, yet many patients do not respond to current therapies. This novel vaccine strategy may prime a patient's immune system against their tumor and work synergistically with immunotherapy against advanced-stage melanoma.

Methods: This was a prospective, randomized, double-blind, placebo-controlled, phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine administered to prevent recurrence in patients with resected stage III/IV melanoma. Patients were enrolled and randomized 2:1 to the TLPLDC vaccine or placebo (empty yeast cell wall particles and autologous dendritic cells). Both intention-to-treat (ITT) and per treatment (PT) analyses were predefined, with PT analysis including patients who remained disease-free through the primary vaccine/placebo series (6 months).

Results: A total of 144 patients were randomized (103 vaccine, 41 control). Therapy was well-tolerated with similar toxicity between treatment arms; one patient in each group experienced related serious adverse events. While disease-free survival (DFS) was not different between groups in ITT analysis, in PT analysis the vaccine group showed improved 24-month DFS (62.9% vs. 34.8%, p = 0.041).

Conclusions: This phase IIb trial of TLPLDC vaccine administered to patients with resected stage III/IV melanoma shows TLPLDC is well-tolerated and improves DFS in patients who complete the primary vaccine series. This suggests patients who do not recur early benefit from TLPLDC in preventing future recurrence from melanoma. A phase III trial of TLPLDC + checkpoint inhibitor versus checkpoint inhibitor alone in patients with advanced, surgically resected melanoma is under development.

Trial registration: NCT02301611.

Conflict of interest statement

This clinical study was sponsored by Elios Therapeutics, a wholly-owned subsidiary of Perseus Holdings, USA. which provided funding to the institution of Dr. Robert Andtbacka; Dr. James Jakub is a Advisory Board Member of a Melanoma Surgical Advisory Board, Norvartis Oncology; Dr. Thomas Wagner is an employee of Orbis Health Solutions; Dr. George Peoples is a part-time employeed of Orbis Health Solutions, has consulted for a number of companies broadly in the cancer vaccine space (none working in melanoma or with autologous DC-based vaccines), and has multiple patents for different versions of cancer vaccines, mostly peptide-based vaccines; Dr. Wagner is the inventor on several patents on the technology of the study. Timothy J. Vreeland, Guy T. Clifton, Diane F. Hale, Robert C. Chick, Annelies T. Hickerson, Jessica L. Cindass, Alexandra M. Adams, Phillip M. Kemp Bohan, Adam C. Berger, Jeffrey J. Sussman, Alicia M. Terando, and Mark B. Faries have no conflicts of interest to declare.

© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Figures

Fig. 1

CONSORT diagram demonstrating patient flow through screening, randomization, treatment, and follow-up. ITT intention-to-treat, TLPLDC tumor lysate, particle-loaded, dendritic cell, PT per treatment

Fig. 2

Kaplan–Meier curves demonstrating 24- and 36-month disease-free survival comparing TLPLDC versus placebo in the (a) ITT analysis and (b) PT analysis. A summary of the survival table is included beneath each Kaplan–Meier curve. TLPLDC tumor lysate, particle-loaded, dendritic cell, ITT intention-to-treat, PT per treatment

Fig. 3

Kaplan–Meier curve demonstrating 24-month overall survival comparing TLPLDC versus placebo in the ITT analysis. A summary of the survival table is included beneath the Kaplan–Meier curve. TLPLDC tumor lysate, particle-loaded, dendritic cell, ITT intention-to-treat