Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study
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 si...
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| Language: | English |
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e000342.full |
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| author | Sung-Bae Kim Hope S Rugo Sara A Hurvitz Hong-Tai Chang Chiun-Sheng Huang Su-Hua Lee Jung-Tung Hung Shir-Hwa Ueng Shin-Cheh Chen Alice L Yu Ling-Ming Tseng Louis W C Chow Ming-Feng Hou Richard B Schwab James L Murray Hsien-Kun Chang Chwen-Cheng Chen |
| author_facet | Sung-Bae Kim Hope S Rugo Sara A Hurvitz Hong-Tai Chang Chiun-Sheng Huang Su-Hua Lee Jung-Tung Hung Shir-Hwa Ueng Shin-Cheh Chen Alice L Yu Ling-Ming Tseng Louis W C Chow Ming-Feng Hou Richard B Schwab James L Murray Hsien-Kun Chang Chwen-Cheng Chen |
| author_sort | Sung-Bae Kim |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6edfc74c39b5454884784f7a49c0a626 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-6edfc74c39b5454884784f7a49c0a6262025-08-20T02:13:22ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2019-000342Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled studySung-Bae Kim0Hope S Rugo1Sara A Hurvitz2Hong-Tai Chang3Chiun-Sheng Huang4Su-Hua Lee5Jung-Tung Hung6Shir-Hwa Ueng7Shin-Cheh Chen8Alice L Yu9Ling-Ming Tseng10Louis W C Chow11Ming-Feng Hou12Richard B Schwab13James L Murray14Hsien-Kun Chang15Chwen-Cheng Chen164Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic ofHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA8 Jonsson Comprehensive Cancer Center, Department of Hematology/Oncology, University of California Los Angeles, Los Angeles, California, USA12 Department of Surgery, Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan1 Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan16 Department of Statistics and Biometrics, OBI Pharma Inc, Taipei, TaiwanInstitute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Linkou, Taiwan15 Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Linkou, Taiwan13 Department of General Surgery, Chang Gung Memorial Hospital, Linkou, TaiwanDepartment of Pediatrics, University of California, San Diego, California, USA4 Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan6 UNIMED Medical Institute, Hong Kong, China7 Division of Breast Surgery, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung, Taiwan9 Moores Cancer Center, University of California San Diego, San Diego, California, USA10 Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA11 Department of Internal Medicine, Division of Hematology-Oncology, Chang Gung Memorial Hospital, Linkou, Taiwan17 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institute, Taipei, TaiwanPurpose 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.https://jitc.bmj.com/content/8/2/e000342.full |
| spellingShingle | Sung-Bae Kim Hope S Rugo Sara A Hurvitz Hong-Tai Chang Chiun-Sheng Huang Su-Hua Lee Jung-Tung Hung Shir-Hwa Ueng Shin-Cheh Chen Alice L Yu Ling-Ming Tseng Louis W C Chow Ming-Feng Hou Richard B Schwab James L Murray Hsien-Kun Chang Chwen-Cheng Chen Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study Journal for ImmunoTherapy of Cancer |
| title | Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study |
| title_full | Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study |
| title_fullStr | Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study |
| title_full_unstemmed | Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study |
| title_short | Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study |
| title_sort | globo h klh vaccine adagloxad simolenin obi 822 obi 821 in patients with metastatic breast cancer phase ii randomized placebo controlled study |
| url | https://jitc.bmj.com/content/8/2/e000342.full |
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