Tumor lysate particle only vaccine (TLPO) vs. Tumor lysate particle-loaded, dendritic cell vaccine (TLPLDC) to prevent recurrence in resected stage III/IV melanoma patients: Results of a phase I/IIa trial.

Autor: Van Decar SG; Brooke Army Medical Center, San Antonio, TX, USA. Electronic address: spencer.vandecar@gmail.com., Carpenter EL; Brooke Army Medical Center, San Antonio, TX, USA., Adams AM; Brooke Army Medical Center, San Antonio, TX, USA., Chick RC; Brooke Army Medical Center, San Antonio, TX, USA., Clifton GT; Brooke Army Medical Center, San Antonio, TX, USA., Stojadinovic A; Cancer Vaccine Development Program, San Antonio, TX, USA., Vreeland TJ; Brooke Army Medical Center, San Antonio, TX, USA., Valdera FA; Brooke Army Medical Center, San Antonio, TX, USA., Tiwari A; University of Texas Health Sciences Center, San Antonio, TX, USA., O'Shea AE; Brooke Army Medical Center, San Antonio, TX, USA., McCarthy PM; Brooke Army Medical Center, San Antonio, TX, USA., Hale DF; Brooke Army Medical Center, San Antonio, TX, USA., Bohan PMK; Brooke Army Medical Center, San Antonio, TX, USA., Hickerson AT; Brooke Army Medical Center, San Antonio, TX, USA., Cindass JL; Brooke Army Medical Center, San Antonio, TX, USA., Hyngstrom J; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Berger AC; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA., Jakub JW; Mayo Clinic, Jacksonville, FL, USA., Sussman JJ; University of Cincinnati, Cincinnati, OH, USA., Shaheen M; University of Arizona, Tucson, AZ, USA., Yu X; Department of Biological Sciences, Clemson University, Clemson, SC, USA., Wagner T; Orbis Health Solutions, Greenville, SC, USA., Faries MB; The Angeles Clinic, Santa Monica, CA, USA., Peoples GE; Cancer Vaccine Development Program, San Antonio, TX, USA.
Jazyk: angličtina
Zdroj: Cancer treatment and research communications [Cancer Treat Res Commun] 2024 Sep 11; Vol. 41, pp. 100843. Date of Electronic Publication: 2024 Sep 11.
DOI: 10.1016/j.ctarc.2024.100843
Abstrakt: Background: The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from dendritic cells (DC) loaded ex vivo with autologous tumor lysate (TL). TLPLDC has been shown to decrease recurrence in resected Stage III/IV melanoma patients in a Phase IIb trial. The TL particle only (TLPO) vaccine is produced by loading of yeast cell wall particles with autologous TL and direct injection allowing for in vivo DC loading. We have compared the TLPO and TLPLDC vaccines in an embedded Phase I/IIa trial of a larger Phase IIb trial of the TLPLDC vaccine.
Methods: Patients rendered clinically disease-free after surgery were randomized 2:1 to receive the TLPO or TLPLDC vaccine and followed for recurrence and death. Patients had scheduled intradermal inoculations at 0, 1, 2, 6, 12, and 18 months after enrollment. Kaplan-Meier and log-rank analysis were used to compare disease-free survival (DFS) and overall survival (OS) in an intention-to-treat (ITT) analysis.
Results: Sixty-three patients were randomized, 43 TLPO and 20 TLPLDC. Patients randomized to the TLPO arm were more likely to be female (37.2% vs. 10.0 %, p = 0.026), but otherwise no significant clinicopathological differences were identified. No differences in related adverse events (AE) were found between treatment arms. At a median follow-up of 20.5 months, the DFS (60.8% vs. 58.7 %, p = 0.714) and OS (94.6% vs. 93.8 %, p = 0.966) were equivalent between the TLPO and TLPLDC groups, respectively. No statistical differences were found in subgroup analyses between vaccine types, which accounted for receipt of immunotherapy and the use of G-CSF pre-blood draw.
Conclusions: In a randomized, double-blind Phase I/IIa trial, there were no differences in DFS or OS in resected Stage III/IV melanoma patients receiving adjuvant TLPO versus TLPLDC vaccines. Given manufacturing advantages, further efficacy testing of TLPO is warranted in a Phase III trial.
Competing Interests: Declaration of competing interest Dr. Faries is an advisor for Bristol-Myers Squibb, Sanofi, Array Bioscience and Pulse Bioscience. Dr. Wagner is an employee of Orbis Health Solutions. Dr. Peoples is employed by Orbis Health Solutions and Cancer Insight; is a consultant for Rapamycin Holdings, Heat Biologics, Abexxa Biologics, and Pelican Therapeutics; and has received funding from the above as well as Sellas Life Sciences and Genentech. Dr Jakub served on a Novartis Melanoma Surgical Oncology Advisory Board. Dr. Clifton is employed by Parthenon Therapeutics. All remaining authors have declared no conflicts of interest.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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