1. 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
- Author
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O'Cearbhaill, Roisin E, Deng, Wei, Chen, Lee-May, Lucci, Joseph A, Behbakht, Kian, Spirtos, Nick M, Muller, Carolyn Y, Benigno, Benedict B, Powell, Matthew A, Berry, Emily, Tewari, Krishnansu S, Hanjani, Parviz, Lankes, Heather A, Aghajanian, Carol, and Sabbatini, Paul J
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Clinical Trials and Supportive Activities ,Immunization ,Cancer ,Vaccine Related ,Rare Diseases ,Clinical Research ,Prevention ,Pediatric Research Initiative ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adjuvants ,Immunologic ,Adult ,Aged ,Aged ,80 and over ,Cancer Vaccines ,Carcinoma ,Ovarian Epithelial ,Double-Blind Method ,Fallopian Tube Neoplasms ,Female ,Hemocyanins ,Humans ,Middle Aged ,Neoplasm Staging ,Ovarian Neoplasms ,Peritoneal Neoplasms ,Vaccines ,Conjugate ,Randomized ,Vaccine ,Ovarian ,Remission ,OPT-821 ,Oncology and Carcinogenesis ,Paediatrics and Reproductive Medicine ,Oncology & Carcinogenesis - Abstract
ObjectiveEarly-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.MethodsFrom 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.ResultsOf 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.ConclusionsVaccine + 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 registrationNCT00857545.
- Published
- 2019