. 2021 Jan 18;20(3):217–243. doi: 10.1038/s41573-020-00093-1

Table 1.

Selected clinical trials of glycobiology-targeted therapeutics^a

Therapeutic type and name; manufacturer	Indication	Phase and status	Results	Trial identifiers (refs)
*Pan-selectin antagonists*
Small molecule Cylexin (CY-1503); Cytel	Ischaemia–reperfusion injury in infant heart surgery	Phase II/III completed 2001	NR	NCT00226369
Small molecule Rivipansel (GMI-1070); GlycoMimetics	Vaso-occlusive crisis in sickle cell disease	Phase I/II completed 2010	Well tolerated, no adverse events	NCT00911495 (ref.²⁷⁵)
	Vaso-occlusive crisis in sickle cell disease and S-β-thalassaemia	Phase II completed 2013	Trend towards reduced time to vaso-occlusive crisis resolution	NCT01119833
	Vaso-occlusive crisis in sickle cell disease	Phase III completed 2019	Post hoc analysis showed efficacy in a subset of patients	NCT02187003 (ref.⁴⁴)
Small molecule Bimosiamose (TBC-1269); Texas Biotechnology Corporation	Psoriasis (as a cream)	Phase II completed 2009	NR	NCT00823693
	Ozone-induced sputum neutrophilia	Phase II completed 2010	NR	NCT00962481
	Chronic obstructive pulmonary disease	Phase II completed 2011	Attenuates airway inflammation	NCT01108913 (refs^51,276)
Small molecule Sevuparin; Modus Therapeutics	Vaso-occlusive crisis in sickle cell disease	Phase II completed 2019	NR	NCT02515838
*P-selectin antagonists*
Small molecule PSI-697; Wyeth and Pfizer	Scleritis	Phase I terminated 2007	NR (terminated)	NCT00367692
Biologic (decoy ligand) YSPSL (rPSGL–Ig); Genetics Institute and Wyeth	Delayed graft function during kidney allograft	Phase I/IIa completed 2007	Safe, no effect on renal function	NCT00298181 (ref.⁶⁶)
	Delayed graft function during kidney allograft	Phase I/IIb completed 2007	Attenuated biomarkers of inflammation	NCT00298168 (refs^66,277)
	Ischaemia–reperfusion injury during liver allograft	Phase II completed 2009	Safe, measures of graft function trended towards improvement, liver enzymes normalized	NCT00876902 (ref.⁶⁵)
	Delayed graft function during liver allograft	Phase II completed 2008	NR	NCT00450398
Monoclonal antibody Inclacumab (anti-P-selectin; RO4905417); Hoffman–La Roche	Myocardial infarction	Phase II completed 2012	Reduced myocardial damage (troponin I levels) in NSTEMI patients	NCT01327183 (refs^68,278)
	Coronary heart disease graft occlusion	Phase II completed 2013	No effect on saphenous vein graft failure, possibly because prior activation of P-selectin pathway not evaluated	NCT01245634 (ref.⁶⁹)
Monoclonal antibody Crizanlizumab (anti-P-selectin; SEG101 or SelG1); Selexys and Novartis	Vaso-occlusive crises in sickle cell disease	Phase II completed 2016	Reduced rate of vaso-occlusive crises and time to first crisis	NCT01895361 (ref.⁷⁰)
	Vaso-occlusive crises in sickle cell disease	Phase II ongoing	Estimated completion in 2021	NCT03264989
	PK in paediatric patients with sickle cell disease	Phase II ongoing	Estimated completion in 2023	NCT03474965
	Vaso-occlusive crises in sickle cell disease in adolescents and adults	Phase III ongoing	Estimated completion in 2027	NCT03814746
	Sickle cell disease related priapism	Phase II ongoing	Estimated completion in 2022	NCT03938454
	Chronic kidney disease in sickle cell disease patients	Phase II ongoing	Estimated completion in 2022	NCT04053764
	Myelofibrosis (combination treatment with ruxolitinib)	Phase I/II ongoing	Estimated completion in 2024	NCT04097821
*E-selectin antagonists*
Small molecule Uproleselan (GMI-1271); GlycoMimetics	Deep vein thrombosis	Phase I/II terminated 2016	NR (terminated with grant expiration)	NCT02744833
	Multiple myeloma	Phase I completed 2019	NR	NCT02811822
	Acute myeloid leukaemia	Phase II/III and III ongoing	Estimated completion in 2023	NCT03616470, NCT03701308
*Siglec antibody–drug conjugates*
Gemtuzumab ozogamicin (Mylotarg; anti-CD33–calicheamicin conjugate); Wyeth and Pfizer	Acute myeloid leukaemia	Phase II completed 2000	Improved survival with reasonable safety profile; FDA approval granted	Trials 201, 202, 203 (refs^279,280)
	Acute myeloid leukaemia	Phase III completed 2014	No survival benefit and higher rates of fatal toxicity; removed from US market in 2010	NCT00085709 (ref.²⁸¹)
	Acute myeloid leukaemia	Phase III completed 2013	Lower doses of drug on new dosing schedule improved outcomes without increasing death from toxicity; FDA approval in 2017	NCT00927498 (refs^282,283)
Inotuzumab ozogamicin (Besponsa; anti-CD22–calicheamicin conjugate); Pfizer	Acute lymphoblastic leukaemia	Phase III completed 2017	Improved progression-free and overall survival	NCT01564784 (ref.¹⁰²)
Pinatuzumab vedotin (anti-CD22–MMAE conjugate); Genentech and Hoffman–La Roche	Follicular lymphoma and diffuse large B cell lymphoma	Phase I/II completed 2019	Achieved objective responses, but development shelved in favour of other more robust therapies	NCT01691898 (ref.¹⁰³)
*CD33 antagonists*
Monoclonal antibody AL003; Alector	Alzheimer disease	Phase I ongoing	Estimated completion in 2021	NCT03822208
*Siglec-8 agonists*
Monoclonal antibody Lirentelimab (AK002); Allakos	Keratoconjunctivitis, vernal conjunctivitis, allergic conjunctivitis	Phase I completed 2019	NR	NCT03379311
	Eosinophilic gastritis, eosinophilic gastroenteritis	Phase II completed 2019	Reduced gastrointestinal eosinophil count and symptoms in a majority of patients	NCT03496571 (ref.¹⁷²)
	Chronic urticaria	Phase II completed 2020	Estimated completion in 2020	NCT03436797
	Eosinophilic gastroenteritis	Phase II ongoing	Estimated completion in 2021	NCT03664960
	Eosinophilic oesophagitis	Phase II/III ongoing	Estimated completion in 2022	NCT04322708
	Eosinophilic gastritis, eosinophilic duodenitis	Phase III ongoing	Estimated completion in 2021	NCT04322604
*Siglec-10 agonists*
Recombinant ligand CD24Fc; OncoImmune	Severe COVID-19	Phase III ongoing	Estimated completion in 2020	NCT04317040
	Immune-related adverse events associated with checkpoint inhibitors	Phase I/II not yet recruiting	Estimated completion in 2023	NCT04060407
	Acute graft-versus-host disease	Phase III not yet recruiting	Estimated completion in 2024	NCT04095858
*Siglec-15 antagonists*
Monoclonal antibody NC318; NextCure	Metastatic solid tumours, head and neck squamous cell carcinoma, NSCLC, ovarian cancer, triple-negative breast cancer	Phase I/II ongoing	Estimated completion in 2021; NSCLC and ovarian cancer cohorts will not advance after interim analysis	NCT03665285 (ref.²⁸⁴)
*Mammalian glycan vaccines*
Carbohydrate vaccine Theratope (sTn–KLH vaccine); Biomira	Breast cancer	Phase III completed 2008	No benefit to overall survival or time to progression; post hoc analysis showed benefit when combined with endocrine therapy	NCT00003638 (refs^226,285)
Peptide vaccine MUC1 peptide plus poly-ICLC; University of Pittsburgh	Colorectal adenoma	Phase II ongoing	Patients produced anti-MUC1 IgG; adenoma recurrence data pending	NCT02134925
	Lung carcinoma	Phase I ongoing	Estimated completion in 2020	NCT03300817
Adenoviral vaccine ETBX-011 (Ad5 CEA vaccine); Etubics and NCI	Colorectal carcinoma	Phase I/II completed 2013	Generated T cell response to CEA	NCT01147965 (ref.²⁸⁶)
Adenoviral vaccine ETBX-011/ETBX-061/ETBX-051 (Ad5 CEA/MUC1/brachyury vaccine); Etubics and NCI	Colon, breast, lung and prostate cancers	Phase I ongoing	Generated T cell response to CEA, MUC1 and brachyury	NCT03384316 (ref.²²²)
Carbohydrate vaccine BMS-248479 (GM2–KLH/QS-21 vaccine); Bristol-Myers-Squibb	Melanoma	Phase III terminated 2007	Terminated for futility	NCT00005052 (ref.²¹¹)
Carbohydrate vaccine Trivalent (GM2/GD2/GD3–KLH) vaccine with OPT-821; MabVax	Metastatic sarcoma	Phase II completed 2013	No benefit, trend towards reduced progression-free survival	NCT01141491
Carbohydrate vaccine Globo H–GM2–sTn–TF–Tn–KLH conjugate/QS-21 vaccine; Memorial Sloan Kettering Cancer Center	Fallopian tube, ovarian and peritoneal cancers	Phase I completed 2017	Most patients developed serologic response to at least three antigens in vaccine	NCT01248273 (ref.²²⁸)
Carbohydrate mimetic peptide vaccine P10s-PADRE vaccine; University of Arkansas	Breast cancer	Phase I completed 2019	Serologic response to Le^y and GD2 in all subjects	NCT01390064 (ref.²²⁹)
Carbohydrate vaccine GD2/GD3 lactone–KLH/OPT-821 vaccine; Memorial Sloan Kettering Cancer Center	Neuroblastoma	Phase I/II ongoing	Estimated completion in 2020	NCT00911560 (ref.²³¹)
Carbohydrate vaccine Adagloxad simolenin (OPT-822; Globo H–KLH/QS-21 vaccine); OBI Pharma and Memorial Sloan Kettering Cancer Center	Breast cancer	Phase II/III completed 2019	No improvement in survival; progression-free and overall survival did improve in patients with serologic response	NCT01516307 (ref.²¹⁵)
	Triple-negative breast cancer	Phase III ongoing	Estimated completion in 2025	NCT03562637
Carbohydrate vaccine sLe^a–KLH conjugate/QS-21; Memorial Sloan Kettering Cancer Center	Breast cancer	Pilot study completed 2020	Estimated completion in 2020	NCT00470574
*Anti-glycan antibodies*
Monoclonal antibody Oregovomab (anti-MUC16/CA125; B43.13); ViRexx Medical Corp	Ovarian cancer	Phase III terminated 2007	No clinical benefit as a monotherapy following frontline carboplatin–paclitaxel treatment	NCT00050375 (ref.²⁸⁷)
	Ovarian neoplasms	Phase II completed 2018	Administered with carboplatin–paclitaxel treatment; improved overall survival, likely related to increased CA125-specific T cells	NCT01616303^288,289
	Ovarian, fallopian tube and peritoneal carcinomas	Phase III ongoing	Estimated completion in 2027	NCT04498117
Monoclonal antibody BIW-8962 (anti-GM2); Kyowa Hakko Kirin Pharma, Inc.	Multiple myeloma	Phase I terminated 2011	Terminated for lack of efficacy	NCT00775502 (ref.²⁹⁰)
	NSCLC, small cell lung cancer, mesothelioma	Phase I/II terminated 2016	Terminated for lack of efficacy	NCT01898156
Monoclonal antibody Dinutuximab (ch14.18; anti-GD2); Scripps Research Institute	Neuroblastoma	Phase III completed 2012	Improved event-free and overall survival	NCT00026312 (ref.²³⁸)
Monoclonal antibody MORAb-028 (anti-GD2 IgM); Morphotek	Melanoma	Phase I terminated 2012	Terminated for lack of drug availability	NCT01123304
Monoclonal antibody Ecromeximab (KW2871; anti-GD3); Kyowa Hakko Kirin Pharma, Inc.	Metastatic melanoma	Phase II completed 2014	Limited efficacy with high-dose interferon, possibly because tumour burdens in the population studied were already high	NCT00679289 (ref.²⁹¹)
Monoclonal antibody BMS-986012 (anti-Fuc-GM1); Bristol-Myers-Squibb	Relapsed and refractory small cell lung cancer	Phase I/II ongoing	Estimated completion in 2020	NCT02247349
Monoclonal antibody OBI-888 (anti-globo H); OBI Pharma	Solid tumours	Phase I/II ongoing	Estimated completion in 2021	NCT03573544
Antibody drug conjugate OBI-999 (anti-globo H–MMAE conjugate); OBI Pharma	Solid tumours	Phase I/II ongoing	Estimated completion in 2023	NCT04084366
Monoclonal antibody MVT-5873 (clone 5B1 anti-CA19-9); MabVax Therapeutics	Pancreatic cancer	Phase I ongoing	Estimated completion in 2020	NCT02672917
Radiolabelled monoclonal antibody MVT-1075 (¹⁷⁷Lu 5B1 anti-CA19-9); MabVax Therapeutics	Pancreatic cancer, tumours expressing CA19-9	Phase I ongoing	Estimated completion in 2020	NCT03118349
Radiolabelled monoclonal antibody MVT-2163 (⁸⁹Zr-DFO-5B1 anti-CA19-9) with MVT-1075 for PET imaging; MabVax Therapeutics	Pancreatic cancer, tumours expressing CA19-9	Phase I ongoing	Estimated completion in 2020	NCT02687230
*Anti-idiotype antibodies*
Monoclonal antibody Abagovomab (anti-MUC16/CA125); Menarini Group	Ovarian cancer	Phase II/III terminated 2011	Administered as maintenance therapy; no clinical benefit and no induction of CA125-specific T cells	NCT00418574 (refs^292,293)
Monoclonal antibody Racotumomab (anti-N-glycolyl-GM3); Recombio	NSCLC	Phase III completed 2014	Increased progression-free and overall survival Serological response to N-glycolyl-GM3	NCT01460472 (ref.²⁹⁴)
	Tumours with N-glycolylated gangliosides: neuroblastoma, Ewing’s sarcoma, Wilm’s tumour, retinoblastoma, glioma	Phase I completed 2014	Well tolerated, serological response to N-glycolyl-GM3 in most patients	NCT01598454 (ref.²⁹⁵)
	Neuroblastoma	Phase II recruiting	Estimated completion in 2021	NCT02998983
*CAR cell therapies*
Anti-GD2 CAR T; Baylor College of Medicine	Neuroblastoma	Phase I ongoing	3 of 11 patients achieved completion remission; study completion estimated in 2021	NCT00085930 (ref.²⁹⁶)
Anti-GD2 CAR T with iCaspase switch; Baylor College of Medicine	Neuroblastoma	Phase I ongoing	Estimated completion in 2030	NCT01822652
Anti-GD2 tri-virus CAR T; Baylor College of Medicine	Neuroblastoma after haematopoietic stem cell transplant	Phase I completed 2015	Safe, partial response in 3 of 3 patients	NCT01460901
Anti-GD2 CAR NKT; Baylor College of Medicine	Neuroblastoma	Phase I ongoing	Estimated completion 2021	NCT03294954

Ad5, adenovirus serotype 5; CAR, chimeric antigen receptor; CEA, carcinoembryonic antigen; KLH, keyhole limpet haemocyanin; Le^y, Lewis^y; MMAE, monomethyl auristatin E; MUC1, mucin 1; NCI, National Cancer Institute; NR, not reported; NSCLC, non-small cell lung cancer; NSTEMI, non-ST elevation myocardial infarction; PADRE, pan-HLA DR binding-epitope; PET, positron emission tomography; PK, pharmacokinetics; poly-ICLC, polyinosinic–polycytidylic acid stabilized with polylysine and carboxymethylcellulose; rPSGL–Ig, recombinant PSGL1 fused to immunoglobulin; sLe^a, sialyl Lewis^a; sTn, sialyl-Tn; TF, Thomsen–Friedenreich antigen. ^aOnly trials registered at ClinicalTrials.gov are included.