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.

Trial registration: NCT00857545.

Keywords: OPT-821; Ovarian; Randomized; Remission; Vaccine.

Conflict of interest statement

CONFLICTS OF INTEREST

The authors wish to report that they have no Conflicts of interest with the exception of Dr. O’Cearbhaill who wishes to report that she has received personal fees from Clovis for serving on an Advisory Board in 2016, from Tesaro for serving on an Advisory Board in both 2017 and 2018 and from GlaxoSmithKline for serving on an Advisory Board in 2019, outside the submitted work. Dr. Benigno wishes to report that he is a member of the Speaker Bureau for AstraZeneca, Tesaro and Clovis. Dr. Powell reports personal fees from Tesaro, personal fees from Merck, personal fees from Roche/Genentech, personal fees from Clovis Oncology, personal fees from AstraZeneca and personal fees from Johnson & Johnson, outside the submitted work. Dr. Aghajanian reports personal fees from Tesaro, personal fees from Immunogen, personal fees from Clovis, personal fees from Mateon Therapeutics, personal fees from Cerulean Pharma, outside the submitted work. Dr. Sabbatini reports grants from BMS, during the conduct of the study.

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

Figure 1.

Kaplan-Meier curves of progression-free survival (PFS) for Vaccine KLH + OPT-821 versus OPT-821 alone

Figure 2.

Kaplan-Meier curves of overall survival for Vaccine KLH + OPT-821 versus OPT-821 alone

Figure 3.

(Available online only) Kaplan-Meier curves of PFS for Vaccine KLH + OPT-821 versus OPT-821 alone by complete remission status

Figure 4.

Kaplan-Meier curves of PFS for Vaccine KLH + OPT-821 versus OPT-821 alone by prior bevacizumab (BEV) treatment