Abstract OT1-08-03: Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of adagloxad simolenin (OBI-822) and OBI-821 treatment in patients with early-stage triple-negative breast cancer (TNBC) at high risk for recurrence
Authors: Rugo Hope S , Chow Louis WC , Cortes Javier , Fasching Peter A , Xu Binghe , Huang Chiun-Sheng , Kim Sung-Bae , Lu Yen-Shen , Nanda Rita , Sharma Priyanka , Schwab Richard B , Tsai Chen-En 
Published: March 2020

Abstract
Background: Adagloxad simolenin (AS) is an investigational immune stimulant comprising the Globo H hexasaccharide epitope linked to the carrier protein keyhole limpet hemocyanin (KLH). KLH facilitates a more vigorous immune response given the weak antigen, Globo H. Furthermore, AS is co-administered with the potent saponin-based adjuvant OBI-821 to induce a humoral response. A phase 2 trial examining the correlation between Globo H expression and clinical outcomes showed that patients with metastatic breast cancer whose tumors had an H-score of ≥15 (validated immunohistochemical [IHC] assay to determine Globo H expression; range 0-300) treated with AS/OBI-821 had a trend for superior progression-free survival vs placebo. As previously reported, Globo H is expressed similarly among both hormone receptor-positive and triple-negative breast cancer tumor subtypes. In an effort to improve outcomes in TNBC, we are conducting a randomized phase 3 trial in this high-risk population.
Study Aim: The primary objective is to determine the effect of AS/OBI-821 on invasive disease recurrence and disease-free survival in patients with TNBC at high risk for recurrence. Secondary objectives are to determine the impact of AS/OBI-821 on overall survival, quality of life (QoL), breast cancer-free interval, distant disease recurrence and disease-free survival, safety, and tolerability.
Methods. Eligible patients will have TNBC (estrogen receptor/progesterone receptor &lt;5%; HER2-negative) with nonmetastatic disease and 1) either residual invasive disease ≥1 cm in breast or ≥1 positive axillary node following neoadjuvant chemotherapy; or 2) ≥4 axillary lymph nodes with invasive carcinoma treated with adjuvant chemotherapy. Tumors must express Globo H (H-score ≥15 by central laboratory analysis using a validated IHC assay). Eligible patients will receive either AS/OBI-821 or placebo (randomized 1:1), administered as subcutaneous (SC) injections in a double-blind manner. Up to 21 SC injections of study treatment (AS/OBI-821 given as 30 μg AS [OBI-822] in combination with 100 μg OBI-821) or placebo (volume-matched placebo with sucrose and trehalose), with either AS/OBI-821 or placebo will be administered over 100 weeks: weekly for 4 doses, every 2 weeks for 4 doses, every 4 weeks for 4 doses, and then every 8 weeks for 9 doses. All patients will be followed for invasive disease recurrence and overall survival for a maximum of 5 years after randomization.
Patients will be followed every 26 weeks for disease recurrence during the follow-up period until a total of 187 endpoint events (either disease recurrence or death) are reached or the last patient has been followed for 3 years after randomization. Enrolled patients will undergo imaging (baseline, weeks 28, 52, 76, 104, 130, 156, 208, 260) and clinical examination every 3 months for 2 years and every 6 months thereafter. QOL will be assessed (weeks 1, 28, 52, 76, 104, 130, 156, 208, 260) using the EORTC QLQ-C30 plus additional EORTC QLQ-BR23 for breast cancer and European Quality of Life 5 Dimensions 5 Levels questionnaire. Adverse events will be graded/recorded by investigators as per National Cancer Institute CTCAE v5.0. Blood/tumor tissue samples will be collected for exploratory assessments during/after end of trial.
Present and target accrual: Approximately 110 study centers across Europe, North America, and Asia-Pacific will enroll an estimated 668 patients. Patients will be treated for up to 2 years and followed until occurrence of 187 events (invasive disease recurrence or death) or 3 years from last patient randomized. Survival follow-up is for 5 years from randomization of last patient.
Citation Format: Hope S Rugo, Louis WC Chow, Javier Cortes, Peter A Fasching, Binghe Xu, Chiun-Sheng Huang, Sung-Bae Kim, Yen-Shen Lu, Rita Nanda, Priyanka Sharma, Richard B Schwab, Chen-En Tsai. Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of adagloxad simolenin (OBI-822) and OBI-821 treatment in patients with early-stage triple-negative breast cancer (TNBC) at high risk for recurrence [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-08-03.