TY - JOUR T1 - Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2019-000342 VL - 8 IS - 2 SP - e000342 AU - Chiun-Sheng Huang AU - Alice L Yu AU - Ling-Ming Tseng AU - Louis W C Chow AU - Ming-Feng Hou AU - Sara A Hurvitz AU - Richard B Schwab AU - James L Murray AU - Hsien-Kun Chang AU - Hong-Tai Chang AU - Shin-Cheh Chen AU - Sung-Bae Kim AU - Jung-Tung Hung AU - Shir-Hwa Ueng AU - Su-Hua Lee AU - Chwen-Cheng Chen AU - Hope S Rugo Y1 - 2020/07/01 UR - http://jitc.bmj.com/content/8/2/e000342.abstract N2 - Purpose This randomized, double-blind, placebo-controlled, parallel-group, phase II trial assessed the efficacy and safety of adagloxad simolenin (OBI-822; a Globo H epitope covalently linked to keyhole limpet hemocyanin (KLH)) with adjuvant OBI-821 in metastatic breast cancer (MBC).Methods At 40 sites in Taiwan, USA, Korea, India, and Hong Kong, patients with MBC of any molecular subtype and ≤2 prior progressive disease events with stable/responding disease after the last anticancer regimen were randomized (2:1) to adagloxad simolenin (AS/OBI-821) or placebo, subcutaneously for nine doses with low-dose cyclophosphamide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, correlation of clinical outcome with humoral immune response and Globo H expression, and safety.Results Of 349 patients randomized, 348 received study drug. Patients with the following breast cancer subtypes were included: hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) (70.4%), triple negative (12.9%), and HER2+ (16.7%), similarly distributed between treatment arms. Median PFS was 7.6 months (95% CI: 6.5–10.9) with AS/OBI-821 (n=224) and 9.2 months (95% CI: 7.3–11.3) with placebo (n=124) (HR=0.96; 95% CI: 0.74–1.25; p=0.77), with no difference by breast cancer subtype. AS/OBI-821 recipients with anti-Globo H IgG titer ≥1:160 had significantly longer median PFS (11.1 months (95% CI: 9.3–17.6)) versus those with titers <1:160 (5.5 months (95% CI: 3.7–5.6); HR=0.52; p<0.0001) and placebo recipients (HR=0.71; p=0.03). Anti-KLH immune responses were similar at week 40 between AS/OBI-821 recipients with anti-Globo IgG titer ≥1:160 and those with anti-Globo IgG titer <1:160. The most common adverse events with AS/OBI-821 were grade 1 or 2 injection site reactions (56.7%; placebo, 8.9%) and fever (20.1%; placebo, 6.5%).Conclusion AS/OBI-821 did not improve PFS in patients with previously treated MBC. However, humoral immune response to Globo H correlated with improved PFS in AS/OBI-821 recipients, leading the way to further marker-driven studies. Treatment was well tolerated.NCT01516307. ER -