Global Phase 3 Study of AdagloxadSimolenin (OBI-822) and OBI-821 Versus PlaceboTreatment for High Risk Early Stage Triple NegativeBreast Cancer Patients (TNBC) Following Neoadjuvant orAdjuvant Chemotherapy

ABSTRACT

Background: Triple-negativebreast cancer (TNBC) has the highest rate of distant metastasis and poorestoverallsurvival among all breast cancer subtypes. Adagloxad simolenin (AS;OBI-822)is a therapeutic vaccine comprisingthe synthetically manufactured tumor-associatedantigen Globo H linked to the carrier protein keyhole limpethemocyanin (KLH).The KLH provides antigenic immune recognition and T-cell responses. AS isco-administered witha saponin-based adjuvant OBI-821 to induce a humoralresponse. A phase 2 trial showed that AS/OBI-821exhibiteda trend for superior progression-free survival vs placebo in patientswhose breast cancers had higher GloboHexpression. Administrationof AS/OBI-821 resulted in IgM and IgG anti-Globo H humoral response and atrendtowards improved PFS in patients with metastatic breast cancer overexpressingGlobo H. We describe therationale and design of GLORIA, an ongoing Phase III,randomized, open-label study to evaluate efficacy, safety, and quality of life(QoL) of AS plus standard of care (SOC) versus SOC alone in patients with high-risk, early-stage TNBC. The primary endpoint is invasive progression-freesurvival;secondary endpoints include overall survival, QoL, breastcancer-freeinterval, distant disease-free survival, safety, and tolerability. Trial Design: A phase 3 trial was initiated inDecember 2018 and had been slowly enrolling until being put on holddue to theCovid-19 pandemic. While the study wason hold the design waschanged from a placebo-control to astandard-of-care control trial based onfeedback from investigators and leading breast cancer advisers, that thenumberof placebo injections was a serious burden on patients. Furthermore, it wasapparent that blinding wasquestionable given the expected and frequent localskin inflammation and low-grade fevers that accompany theAS/OBI-821 vaccineadministration and the absence of these obvious clinical signs and symptoms with the normalsaline placebo control.The main changes to the protocol are as followsMethods: Eligibility includes patients with TNBC (estrogen receptor/progesterone receptor <5%,and HER2-negative) with nonmetastatic disease and 1) either residual invasive disease of ≥1 cm in breast or ≥1 positiveaxillary node following neoadjuvantchemotherapy;Pathological Stage IIB or III disease treated with adequateadjuvant chemotherapy alone;received ≥4 cycles of standard taxane- and/oranthracycline-basedchemotherapy;randomized within 12 weeks of surgery, adjuvant multi-agent chemotherapy,or radiation therapy.Inaddition, tumors must express Globo H (H-score of ≥15 by central laboratory analysis using a validatedimmunohistochemical assay). Subjects in the AS/OBI-821 group will receive 30 μg of AS in combination with 100 μgofOBI-821.This revised study will start re-enrolling patients as soon as Covid-19 restrictions are lifted with the firstcountry being South Korea with an anticipated start date in Q4/2020.