دورية أكاديمية
أعرض في EDS

Prospective, randomized, double-blind phase 2B trial of the TLPO and TLPLDC vaccines to prevent recurrence of resected stage III/IV melanoma: a prespecified 36-month analysis.

التفاصيل البيبلوغرافية
العنوان: Prospective, randomized, double-blind phase 2B trial of the TLPO and TLPLDC vaccines to prevent recurrence of resected stage III/IV melanoma: a prespecified 36-month analysis.
المؤلفون: Carpenter EL; Surgery, San Antonio Military Medical Center, Fort Sam Houston, Texas, USA., Van Decar S; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA spencer.vandecar@gmail.com., Adams AM; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., O'Shea AE; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., McCarthy P; General Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., Chick RC; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., Clifton GT; Surgery, Uniformed Services University, Bethesda, Maryland, USA.; Surgical Oncology, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., Vreeland T; Surgery, Uniformed Services University, Bethesda, Maryland, USA.; Surgical Oncology, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., Valdera FA; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., Tiwari A; Department of Surgery, University of Texas Health Sciences Center, San Antonio, Texas, USA., Hale D; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA.; Surgery, Uniformed Services University, Bethesda, Maryland, USA., Kemp Bohan P; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., Hickerson A; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., Smolinsky T; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., Thomas K; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., Cindass J; Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA., Hyngstrom J; Surgical Oncology, Huntsman Cancer Institute Cancer Hospital, Salt Lake City, Utah, USA., Berger AC; Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA., Jakub J; Surgery, Mayo Clinic, Jacksonville, Florida, USA., Sussman JJ; Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA., Shaheen MF; Medical Oncology, University of Arizona Medical Center-University Campus, Tucson, Arizona, USA., Yu X; Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA., Wagner TE; Orbis Health Solutions, Greenville, South Carolina, USA., Faries M; Surgical Oncology, Cedars-Sinai Medical Center Angeles Clinic and Research Institute, Los Angeles, California, USA., Peoples GE; Cancer Vaccine Development Program, San Antonio, Texas, USA.
المصدر: Journal for immunotherapy of cancer [J Immunother Cancer] 2023 Aug; Vol. 11 (8).
نوع المنشور: Randomized Controlled Trial; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: Print Cited Medium: Internet ISSN: 2051-1426 (Electronic) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2020- : London, United Kingdom : BMJ Publishing Group Ltd.
Original Publication: London : BioMed Central, 2013-
مواضيع طبية MeSH: Melanoma* , Cancer Vaccines*/therapeutic use, Humans ; Prospective Studies ; Dendritic Cells ; Granulocyte Colony-Stimulating Factor ; Melanoma, Cutaneous Malignant
مستخلص: Background: The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is made by ex vivo priming matured autologous dendritic cells (DCs) with yeast cell wall particles (YCWPs) loaded with autologous tumor lysate (TL). The tumor lysate, particle only (TLPO) vaccine uses autologous TL-loaded YCWPs coated with silicate for in vivo DC loading. Here we report the 36-month prespecified analyses of this prospective, randomized, double-blind trial investigating the ability of the TLPO and TLPLDC (±granulocyte-colony stimulating factor (G-CSF)) vaccines to prevent melanoma recurrence in high-risk patients.
Methods: Patients with clinically disease-free stage III/IV melanoma were randomized 2:1 initially to TLPLDC versus placebo (n=124) and subsequently TLPO versus TLPLDC (n=63). All patients were randomized and blinded; however, the placebo control arm was replaced in the second randomization scheme with another novel vaccine; some analyses in this paper therefore reflect a combination of the two randomization schemes. Patients receiving the TLPLDC vaccine were further divided by their method of DC harvest (with or without G-CSF pretreatment); this was not randomized. The use of standard of care checkpoint inhibitors was not stratified between groups. Safety was assessed and Kaplan-Meier and log-rank analyses compared disease-free (DFS) and overall survival (OS).
Results: After combining the two randomization processes, a total of 187 patients were allocated between treatment arms: placebo (n=41), TLPLDC (n=103), or TLPO (n=43). The allocation among arms created by the addition of patients from the two separate randomization schemes does not reflect concurrent randomization among all treatment arms. TLPLDC was further divided by use of G-CSF in DC harvest: no G-CSF (TLPLDC) (n=47) and with G-CSF (TLPLDC+G) (n=56). Median follow-up was 35.8 months. Only two patients experienced a related adverse event ≥grade 3, one each in the TLPLDC+G and placebo arms. DFS was 27.2% (placebo), 55.4% (TLPLDC), 22.9% (TLPLDC+G), and 60.9% (TLPO) (p<0.001). OS was 62.5% (placebo), 93.6% (TLPLDC), 57.7% (TLPLDC+G), and 94.6% (TLPO) (p=0.002).
Conclusions: The TLPO and TLPLDC (without G-CSF) vaccines were associated with improved DFS and OS in this clinical trial. Given production and manufacturing advantages, the efficacy of the TLPO vaccine will be confirmed in a phase 3 trial.
Trial Registration Number: NCT02301611.
Competing Interests: Competing interests: MF is an advisor for Bristol-Myers Squibb, Sanofi, Array Bioscience and Pulse Bioscience. TEW is an employee of Orbis Health Solutions. GEP 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. JJ served on a Novartis Melanoma Surgical Oncology Advisory Board. GTC is employed by Parthenon Therapeutics. All remaining authors have declared no conflicts of interest.
(© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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فهرسة مساهمة: Keywords: Clinical Trials, Phase II as Topic; Immune Checkpoint Inhibitors; Immunogenicity, Vaccine; Melanoma
سلسلة جزيئية: ClinicalTrials.gov NCT02301611
المشرفين على المادة: 0 (Cancer Vaccines)
143011-72-7 (Granulocyte Colony-Stimulating Factor)
تواريخ الأحداث: Date Created: 20230803 Date Completed: 20230807 Latest Revision: 20231213
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10401209
DOI: 10.1136/jitc-2023-006665
PMID: 37536936
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-1426
DOI:10.1136/jitc-2023-006665