A phase II randomized, double-blind trial of a polyvalent Vaccine-KLH conjugate (NSC 748933 IND# 14384) + OPT-821 versus OPT-821 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer who are in second or third complete remission: An NRG Oncology/GOG study Journal Article


Authors: O'Cearbhaill, R. E.; Deng, W.; Chen, L. M.; Lucci, J. A. 3rd; Behbakht, K.; Spirtos, N. M.; Muller, C. Y.; Benigno, B. B.; Powell, M. A.; Berry, E.; Tewari, K. S.; Hanjani, P.; Lankes, H. A.; Aghajanian, C.; Sabbatini, P. J.
Article Title: A phase II randomized, double-blind trial of a polyvalent Vaccine-KLH conjugate (NSC 748933 IND# 14384) + OPT-821 versus OPT-821 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer who are in second or third complete remission: An NRG Oncology/GOG study
Abstract: Objective: Early-phase data have demonstrated induction of antibody responses to a polyvalent vaccine conjugate (Globo-H, GM2, MUC1-TN, TF) with adjuvant OPT-821. We sought to determine if this combination decreases the hazard of progression or death compared to OPT-821 alone in patients with ovarian cancer in second/third clinical complete remission following chemotherapy. Secondary and translational objectives were overall survival (OS), safety, and immunogenicity. Methods: From 2010-2013, patients were randomized (1:1) to receive OPT-821 +/- vaccine-KLH conjugate subcutaneously at weeks 1, 2, 3, 7, 11, and then every 12 weeks (total 11). Dose delay or reduction was not permitted. Patients were removed for pre-defined dose-limiting toxicity. Results: Of 171 patients randomized, 170 were treated. Most had disease of serous histology (85%), stage 3 disease at diagnosis (77%), and had received 2 prior regimens (68%). 32% received >6 treatment cycles [median 6, each arm (p = 0.33)]. 77% discontinued due to progression, 4% due to toxicity, and 1 due to myeloid dysplastic syndrome (MDS). Maximum toxicities included grade 4 MDS and depression/personality change (1 each, unlikely related), as well as grade 3 gastrointestinal disorders and others (n = 21, 4 related). Lesser adverse events were injection site reactions (82%) and fever (11%). Estimated HR for progression-free survival (PFS) of the vaccine + OPT-821 to OPT-821 arm was 0.98 (95% CI: 0.71-1.36). At a median follow-up of 60 months, median OS was 47 and 46 months, respectively. Conclusions: Vaccine + OPT-821 compared to OPT-821 alone was modestly immunogenic and did not prolong PFS or OS. Multi-remission patients are a viable, well-defined population for exploring innovative consolidation and maintenance approaches. (C) 2019 Elsevier Inc. All rights reserved.
Keywords: survival; chemotherapy; remission; vaccine; randomized; ovarian-cancer; ovarian; consolidation; epithelial ovarian; opt-821
Journal Title: Gynecologic Oncology
Volume: 155
Issue: 3
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2019-12-01
Start Page: 393
End Page: 399
Language: English
ACCESSION: WOS:000504803500002
DOI: 10.1016/j.ygyno.2019.09.015
PROVIDER: wos
PMCID: PMC6900458
PUBMED: 31653510
Notes: Article -- Source: Wos
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  1. Paul J Sabbatini
    226 Sabbatini