A randomized phase II trial of a trivalent ganglioside vaccine targeting GM2, GD2, and GD3 combined with immunological adjuvant OPT-821 versus OPT-821 alone in metastatic sarcoma patients rendered disease-free by surgery

• Type of Material: Article
• Authors: Evan Rosenbaum, Weill-Cornell Medical Center; Rashmi Chugh, University of Michigan; Christopher W. Ryan, Oregon Health and Science University; Mark Agulnik, City of Hope; Mohammed M. Milhem, University of Iowa; Suzanne George, Dana-Farber Cancer Institute; Robin L. Jones, Royal Marsden; Bartosz Chmielowski, University of California, Los Angeles; Brian Andrew Van Tine, Washington University in Saint Louis; Hussein Tawbi, University of Texas, Houston; Anthony D. Elias, University of Colorado, Aurora; William Read, Emory University; G. thomas Budd, Cleveland Clinic; Li-Xuan Qin, Memorial Sloan-Kettering Cancer Center; Eve T. Rodler, University of California, Davis; Joe Hirman, Pacific Northwest Statistical Consulting; Paul Weiden, BioPharma Consulting Services; Cathryn M. Bennett, BioPharma Consulting Services; Philip O. Livingston, MabVax Therapeutics; Govind Ragupathi, Memorial Sloan-Kettering Cancer Center; David Hansen, MabVax Therapeutics; Sandra P. D'Angelo, Weill-Cornell Medical Center; William D. Tap, Weill-Cornell Medical Center; Gary K. Schwarts, Columbia University; Robert G. Maki, University of Pennsylvania; Richard D. Carvajal, Columbia University
• Language: English
• Date: 2022-10-08
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1016/j.ejca.2022.09.003
• Title of Journal or Parent Work: European Journal of Cancer
• Volume: 176
• Start Page: 155
• End Page: 163
• Grant/Funding Information: MabVax Therapeutics provided funding for this study.
• Keywords: Ganglioside; Adjuvant; Vaccine; Sarcoma
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology

Abstract

Background: Recurrence after resection of metastatic sarcoma is common. The gangliosides GM2, GD2 and GD3 are strongly expressed across sarcoma subtypes. We hypothesized that generation of anti-ganglioside antibodies would control micrometastases and improve outcomes in sarcoma patients who were disease-free after metastasectomy. Methods: We conducted a randomized phase II trial of the immunological adjuvant OPT-821 with a KLH-conjugated ganglioside vaccine targeting GM2, GD2 and GD3, versus OPT-821 alone in patients with metastatic sarcoma following complete metastasectomy. Patients received 10 subcutaneous injections at Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68 and 84 and were followed for evidence of recurrent disease. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS) and serologic response. Results: A total of 136 patients were randomized, 68 to each arm. The mean age was 51.2, 52.2% were male, 90.4% had relapsed disease, 86.8% had high-grade tumors, and 14% had ≥ 4 metastases resected. Histologies included leiomyosarcoma (33%), spindle cell sarcoma (14%), undifferentiated pleomorphic sarcoma (13%), osteosarcoma (10%), synovial sarcoma (9%), liposarcoma (9%) and others (12%). Most adverse events (AEs) were Grade ≤ 2 (83.8% and 70.6% in the vaccine and adjuvant arms, respectively). The most common (≥ 20% of patients) were injection site reaction (89.7%), fatigue (44.1%), and pyrexia (27.9%) on the vaccine arm, and injection site reaction (69.1%) on the adjuvant only arm. The one-year RFS rate (34.5% and 34.8% in the vaccine and OPT-821 monotherapy arm, respectively) did not differ between arms (P = 0.725). One-year OS rates were 93.1% and 91.5% in the vaccine and OPT-821 monotherapy arm, respectively (P = 0.578). Serologic responses at week 9 were more frequent on the vaccine arm (96.5% of patients) than in the adjuvant arm (32.8%), and the difference between groups was durable. Conclusions: A sustained serologic response to vaccination was induced with the vaccine, but no difference in recurrence-free or overall survival was observed between treatment arms.