@article {Huange000342, author = {Chiun-Sheng Huang and Alice L Yu and Ling-Ming Tseng and Louis W C Chow and Ming-Feng Hou and Sara A Hurvitz and Richard B Schwab and James L Murray and Hsien-Kun Chang and Hong-Tai Chang and Shin-Cheh Chen and Sung-Bae Kim and Jung-Tung Hung and Shir-Hwa Ueng and Su-Hua Lee and Chwen-Cheng Chen and Hope S Rugo}, title = {Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study}, volume = {8}, number = {2}, elocation-id = {e000342}, year = {2020}, doi = {10.1136/jitc-2019-000342}, publisher = {BMJ Specialist Journals}, abstract = {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{\textendash}) (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{\textendash}10.9) with AS/OBI-821 (n=224) and 9.2 months (95\% CI: 7.3{\textendash}11.3) with placebo (n=124) (HR=0.96; 95\% CI: 0.74{\textendash}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{\textendash}17.6)) versus those with titers \<1:160 (5.5 months (95\% CI: 3.7{\textendash}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.}, URL = {https://jitc.bmj.com/content/8/2/e000342}, eprint = {https://jitc.bmj.com/content/8/2/e000342.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }