Abstract OT-13-10: Global Phase 3 Study of Adagloxad Simolenin (OBI-822) and OBI-821 Versus Placebo Treatment for High Risk Early Stage Triple Negative Breast Cancer Patients (TNBC) Following Neoadjuvant or Adjuvant Chemotherapy
Authors: Rugo Hope , Chow Louis W.C. , Cortes Javier , Fasching Peter A. , He Xu-Bing , Hsu Pei , Huang Chiun-Sheng , Kim Sung-Bae , Lu Yen-Shen , Melisko Michelle , Nanda Rita , Pearce Tillman E , Sharma Priyanka , Schwab Richard 
Published: February 2021

Background: Triple-negativebreast cancer (TNBC) has the highest rate of distant metastasis and poorestoverall survival among all breast cancer subtypes. Adagloxad simolenin (AS; OBI-822)is a therapeutic vaccine comprising the synthetically manufactured tumor-associatedantigen Globo H linked to the carrier protein keyhole limpet hemocyanin (KLH).The KLH provides antigenic immune recognition and T-cell responses. AS isco-administered with a saponin-based adjuvant OBI-821 to induce a humoralresponse. A phase 2 trial showed that AS/OBI-821exhibited a trend for superior progression-free survival vs placebo in patientswhose breast cancers had higher Globo Hexpression. Administrationof AS/OBI-821 resulted in IgM and IgG anti-Globo H humoral response and a trendtowards improved PFS in patients with metastatic breast cancer overexpressingGlobo H. We describe the rationale 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 withhigh-risk, early-stage TNBC. The primary endpoint is invasive progression-freesurvival; secondary endpoints include overall survival, QoL, breast cancer-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 hold due to theCovid-19 pandemic. While the study wason hold the design waschanged from a placebo-control to a standard-of-care control trial based onfeedback from investigators and leading breast cancer advisers, that the numberof placebo injections was a serious burden on patients. Furthermore, it wasapparent that blinding was questionable given the expected and frequent localskin inflammation and low-grade fevers that accompany the AS/OBI-821 vaccineadministration and the absence of these obvious clinical signs and symptomswith the normal saline placebo control.The main changes to the protocol are as follows:

Methods: Eligibility includes patients with TNBC (estrogen receptor/progesterone receptor &lt;5%,and HER2-negative) with nonmetastatic disease and 1) either residual invasive disease of ≥1 cm in breast or ≥1 positive axillary node following neoadjuvantchemotherapy; Pathological Stage IIB or III disease treated with adequateadjuvant chemotherapy alone; received ≥4 cycles of standard taxane- and/oranthracycline-based chemotherapy; randomized within 12 weeks of surgery, adjuvant multi-agent chemotherapy,or radiation therapy.In addition, tumors must express Globo H (H-score of ≥15 by central laboratory analysis using a validated immunohistochemical assay). Subjects in the AS/OBI-821 group will receive 30 μg of AS in combination with 100 μg ofOBI-821.This revised study will start re-enrolling patients as soon as Covid-19 restrictions are lifted with the first country being South Korea with an anticipated start date in Q4/2020.

Citation Format: Hope Rugo, Louis W.C. Chow, Javier Cortes, Peter A. Fasching, Xu-Bing He, Pei Hsu, Chiun-Sheng Huang, Sung-Bae Kim, Yen-Shen Lu, Michelle Melisko, Rita Nanda, Tillman E Pearce, Priyanka Sharma, Richard Schwab. Global Phase 3 Study of Adagloxad Simolenin (OBI-822) and OBI-821 Versus Placebo Treatment for High Risk Early Stage Triple Negative Breast Cancer Patients (TNBC) Following Neoadjuvant or Adjuvant Chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-13-10.