Table 2.

ADCs under clinic trials in the most recent years

ADC name	Tumor target Antibody	Payload DAR	Linker type	Clinical status	ClinicalTrials Identifier Sponsor	Indication	Reference
Targeted cancer
1. Multiple kinds of tumors
Trastuzumab deruxtecan	HER2 Humanized antibody	Deruxtecan (camptothecin)	Cleavable	Phase I	NCT02564900 Daiichi Sankyo Co, Ltd.	Advanced breast and gastric or gastro-esophageal tumors	(Doi et al., 2017)
Lifastuzumab vedotin (LIFA)	NaPi2b (SLC34A2) Humanized IgG1 monoclonal antibody (MNIB2126A)	MMAE	Cleavable VC linker	Phase I	NCT01911598 Genentech, Inc.	Non-small cell lung cancer or platinum-resistant ovarian cancer	(Gerber et al., 2020)
Anetumab ravtansine (BAY 94–9343)	Mesothelin Fully human IgG1 monoclonal antibody	DM4 3–4	Cleavable disulfide linker	Phase I	NCT01439152 Bayer HealthCare Pharmaceuticals	Advanced or metastatic solid tumors	(Hassan et al., 2020)
PF-06664178 (RN927C)	Trop-2 Humanized IgG1	Aur0101 (auristatin derivative) 2	Cleavable C-terminus of heavy chain via an enzymatic process	Phase I	NCT02122146 Pfizer	Advanced or metastatic solid tumors	(King et al., 2018)
IMGN853 Mirvetuximab soravtansine	Folate receptor α	DM4		Phase I	NCT01609556 ImmunoGen, Inc.	Solid tumors	(Moore et al., 2017a)
ABT-414	EGFR Humanized recombinant antibody	MMAF	Non-cleavable MC linker	Phase I/II	NCT01741727 AbbVie	Advanced solid tumors	(Munasinghe et al., 2017)
Telisotuzumab Vedotin (ABBV399)	c-Met Humanized monoclonal antibody	MMAE	Cleavable VC linker	Phase I	NCT02099058 AbbVie Inc.	Advanced solid tumors	(Strickler et al., 2018)
PF-06647263	EFNA4	Calicheamicin		Phase I	NCT02078752 Pfizer	Advanced solid tumors	(Garrido-Lag una et al., 2019)
PF-06263507	5T4 Humanized IgG1 antibody	MMAF 4	Cleavable MC linker	Phase I	NCT01891669 Pfizer	Advanced solid tumors	(Shapiro et al., 2017)
Depatuxizumab mafodotin (ABT-414)	EGFR	MMAF 3–4	Non-cleavable MC linker	Phase I/II	NCT01800695 AbbVie	Advanced solid tumors likely to overexpress EGFR	(Goss et al., 2018)
Enfortumab vedotin (EV)	Nectin-4 Fully humanized IgG1κ monoclonal antibody	MMAE 3–4	Cleavable maleimidocaproyl VC linker	Phase I	NCT02091999 Astellas Pharma and Seattle Genetics	Nectin-4-positive solid tumors	(Rosenberg et al., 2020)
Brentuximab vedotin	CD30 Chimeric IgG1 antibody	MMAE	Cleavable	Phase II	NCT01461538 Seattle Genetics, Inc.	CD30-expressing solid tumors	(Sharman et al., 2019)
Aprutumab Ixadotin (BAY 1187982)	Fibroblast Growth Factor Receptor 2 (FGFR2) fully human monoclonal antibody	Auristatin W	Non-cleavable	Phase I	NCT02368951 Bayer Healthcare	Advanced FGFR2 positive solid tumors	(Kim et al., 2019)
2. Hodgkin’s lymphoma
Brentuximab vedotin	CD30 Monoclonal antibody	MMAE	Cleavable	Phase III	NCT01712490 Millennium Pharmaceuticals and Seattle Genetics	Stage III or IV Hodgkin’s lymphoma	(Suri et al., 2019)
Brentuximab vedotin	CD30	MMAE		Phase II	NCT01569204 Takeda Pharmaceuticals	Advanced classical Hodgkin’s lymphoma	(Eichenauer et al., 2017)
3. Non-Hodgkin lymphoma
IMGN529	CD37 Humanized monoclonal antibody	DM1		Phase I	NCT01534715 ImmunoGen, Inc.	Relapsed/refractory B-cell non-Hodgkin lymphoma	(Stathis et al., 2018)
Pinatuzumab vedotin	CD22 Monoclonal antibody	MMAE	Cleavable	Phase I	NCT01209130 Genentech, Inc.	Relapsed or refractory B-cell non-Hodgkin lymphoma	(Advani et al., 2017)
Coltuximab ravtansine (SAR3419)	CD19 Monoclonal antibody	DM4	Cleavable hindered disulfide bond	Phase II	NCT01472887 Sanofi	Relapsed/refractory diffuse large B-cell lymphoma	(Trnĕný et al., 2018)
Inotuzumab ozogamicin (InO)	CD22 Humanized antibody	Calicheamicin	Cleavable	Phase III	NCT01232556 Pfizer Inc.	Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma	(Dang et al., 2018)
SGN-CD70A	CD70	PBD	Cleavable	Phase I	NCT02216890 Genetics, Inc.	CD70-positive diffuse large B cell lymphoma and mantle cell lymphoma	(Phillips et al., 2019)
Brentuximab vedotin	CD30	MMAE		Phase II	NCT01421667 Genetics, Inc.	Diffuse large B-cell lymphoma	(Bartlett et al., 2017)
Brentuximab vedotin	CD30	MMAE		Phase I/II	NCT02581631 Bristol-Myers Squibb and Seattle Genetics	Relapsed/refractory primary mediastinal large B-cell lymphoma	(Zinzani et al., 2019)
4. Lung cancers
Rovalpituzumab tesirine (SC16LD6.5)	DLL3 Humanized IgG1 monoclonal antibody	SC-DR002	Cleavable	Phase I	NCT01901653 Stemcentrx Inc.	Small-cell lung cancer	(Rudin et al., 2017)
Sacituzumab govitecan	Trop-2 Humanized antibody	SN-38		Phase I	NCT01631552 Immunomedics, Inc.	Small-cell lung cancer	(Gray et al., 2017)
Lorvotuzumab mertansine (IMGN901)	CD56 Humanized monoclonal antibody	DM1	Cleavable disulfide linker	Phase I/II	NCT01237678	Small-cell lung cancer	(Socinski et al., 2017)
Sacituzumab govitecan	Trop-2 Humanized antibody	SN-38		Phase I/II	NCT01631552	Advanced non-small-cell lung cancer	(Heist et al., 2017)
Trastuzumab emtansine (T-DM1)	HER2	DM1	Non-cleavable thioether linker	Phase II		HER2-positive non-small cell lung cancer	(Hotta et al., 2018)
Rovalpituzumab tesirine	DLL3 Humanized IgG1 monoclonal antibody	PBD	Cleavable	Phase I	NCT03086239 AbbVie Inc.	Advanced, recurrent small cell lung cancer	(Udagawa et al., 2019)
Ado-Trastuzumab emtansine (T-DM1)	HER2	DM1	Non-cleavable thioether linker	Phase II	NCT02675829 Genentech	HER2-mutant lung cancer	(Li et al., 2018)
5. Cancers in esophagus, stomach or intestine
Trastuzumab deruxtecan	HER2 Fully humanized IgG1κ monoclonal antibody	DXd 8	Non-cleavable maleimide tetrapeptide linker	Phase II	NCT03329690 Daiichi Sankyo, Inc. and AstraZeneca	HER2-positive gastric cancer	(Shitara et al., 2020)
TAK-264 (MLN0264)	Guanylyl cyclase C Human mAb	MMAE	Cleavable	Phase II	NCT02202759 Millennium Pharmaceuticals Inc.	Metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction	(Almhanna et al., 2017a)
Ado-Trastuzumab Emtansine (T-DM1)	HER2 Humanized monoclonal antibody	DM1	Non-cleavable thioether linker	Phase I	NCT01641939 Roche Ltd, and Genentech, Inc.	HER2-positive advanced gastric cancer	(Chen et al., 2017b)
6. Pancreatic adenocarcinoma
LMB-100	Mesothelin (MSLN) Humanized Fab	Pseudomonas exotoxin A (PE)		Phase I/II	NCT02810418 Bayer AG, Aduro BioTech, and Morphotek Inc.	Advanced pancreatic adenocarcinoma	(Alewine et al., 2020)
TAK-264 (MLN0264)	Guanylyl cyclase C Human monoclonal antibody	MMAE	Cleavable	Phase II	NCT02202785 Millennium Pharmaceuticals, Inc.	Advanced or metastatic pancreatic adenocarcinoma	(Almhanna et al., 2017b)
7. Colorectal cancer
Labetuzumab Govitecan (IMMU-130)	Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) (CD66e) Humanized antibody	SN-38 (camptothecin)		Phase I/II	NCT01605318 Immunomedics. Inc.	Refractory or relapsing metastatic colorectal cancer	(Dotan et al., 2017)
8 Breast cancer
Trastuzumab deruxtecan (T-DXd)	HER2 Humanized antibody	Exatecan derivative (a topoisomerase I inhibitor)	Cleavable peptide linker	Phase Ib	NCT02564900 Daiichi Sankyo. Inc.	HER2-low-expressing advanced breast cancer	(Modi et al., 2020)
Sacituzumab govitecan (IMMU-132)	Trop-2	SN-38		Phase I/II	NCT01631552 David M. Goldenberg	Metastatic triple-negative breast cancer	(Bardia et al., 2017)
Trastuzumab emtansine	HER2 Humanized monoclonal antibody	DM1		Phase III	NCT00829166 Genentech.	HER2-positive advanced breast cancer	(Diéras et al., 2017)
9. Ovarian cancer
Mirvetuximab soravtansine (IMGN853)	Folate receptor α Humanized antibody	DM4	Cleavable disulfide linker	Phase Ib	NCT02606305 ImmunoGen, Inc.	Sensitive ovarian cancer (in combination with carboplatin); FRα-positive, platinum-resistant ovarian cancer (in combination with bevacizumab)	(Moore et al., 2018a; O’Malley et al., 2020)
Mirvetuximab soravtansine (IMGN853)	Folate receptor α Humanized antibody	DM4	Cleavable	Phase I	NCT01609556 ImmunoGen.	Relapsed epithelial ovarian cancer	(Martin et al., 2017)
Lifastuzumab vedotin (DNIB0600A)	NaPi2b Humanized IgG1 monoclonal antibody	MMAE		Phase II	NCT01991210 Genentech, Inc.	Platinum-resistant ovarian cancer	(Banerjee et al., 2018)
Mirvetuximab Soravtansine IMGN853	Folate receptor α Humanized monoclonal antibody	DM4	Cleavable	Phase I	NCT01609556 ImmunoGen.	Platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer	(Moore et al., 2017b)
Mirvetuximab soravtansine (IMGN853)	Folate receptor α Humanized monoclonal antibody	DM4 3–4	Cleavable disulfide linker	Phase III	NCT02631876	Platinum-resistant ovarian cancer	(Moore et al., 2018b)
10. Cervical cancer
Tisotumab Vedotin	Tissue factor (TF) Fully human monoclonal antibody	MMAE	Protease-cleavable linker	Phase I/II	NCT02001623 Genmab A/S	Recurrent or metastatic cervical cancer	(Hong et al., 2020)
11. Renal cell carcinoma
AMG 172	CD27L Fully human IgG1κ monoclonal antibody	DM1 5	Non-cleavable 4-[N-maleimidomethyl] cyclohexane-1-carb oxylate conjugated to lysine residues	Phase I	NCT01497821 Amgen Inc.	Relapsed/refractory renal cell carcinoma
AGS-16M8F and AGS-16C3F	ENPP3 Fully human IgG2a antibodies	MMAF	Non-cleavable	Phase I	NCT01114230 NCT01672775 Agensys, Inc.	Advanced refractory renal cell carcinomas	(Thompson et al., 2018)
SGN-CD70A	CD70	PBD	Cleavable	Phase I	NCT02216890 Genetics, Inc.	CD70-positive metastatic renal cell carcinoma	(Pal et al., 2019)
12. Prostate cancer
PSMA ADC	Prostate-specific membrane antigen (PSMA) Fully human IgG1 monoclonal antibody	MMAE 4	Cleavable VC linker	Phase I	NCT01414283 Progenics Pharmaceuticals, Inc.	Chemotherapy-refractory prostate cancer	(Petrylak et al., 2019)
DSTP3086S	Six-transmembrane epithelial antigen (STEAP1) Humanized IgG1 monoclonal antibody	MMAE	Cleavable	Phase I	NCT01283373 Genentech, Inc.	Metastatic castration-resistant prostate cancer	(Danila et al., 2019)
ASG-5ME	SLC44A4 Fully human IgG2κ monoclonal antibody	MMAE	Cleavable MC-VC linker	Phase I	NCT01228760 NIH/NCI Cancer Center	Metastatic castration-resistant prostate cancer	(McHugh et al., 2019)
PSMA ADC	PSMA Fully human IgG1 monoclonal antibody	MMAE	Cleavable VC linker	Phase II	NCT01695044 Progenics Pharmaceuticals, Inc	Progressive metastatic castration-resistant prostate cancer	(Petrylak et al., 2020)
13. Epithelial cancers
Sacituzumab govitecan (IMMU-132)	Trop-2 Humanized antibody	SN-38 (camptothecin)		Phase I/II	NCT01631552 Immunomedics, Inc.	Diverse epithelial cancers	(Ocean et al., 2017)
14. Melanoma
Glembatumumab vedotin	Glycoprotein NMB Fully human IgG2 monoclonal antibody	MMAE	Cleavable VC linker	Phase II	NCT02302339 Celldex Therapeutics, Inc.	Advanced melanoma	(Ott et al., 2019)
15. Myeloma
AMG 224	BCMA Human IgG1 antibody	DM1	Non-cleavable	Phase I	NCT02561962 Amgen Inc.	Relapsed or refractory multiple myeloma	(Lee et al., 2021)
DFRF4539A	FcRH5 Humanized IgG1 monoclonal antibody	MMAE	Cleavable MC-VC-PABC linker	Phase I	NCT01432353 Genentech, Inc.	Relapsed or refractory multiple myeloma	(Lee et al., 2021)
GSK2857916	B-cell Maturation antigen Humanized IgG1 monoclonal antibody	MMAF	Non-cleavable Protease-resistant MC linker	Phase I	NCT02064387 Glaxo SmithKline.	Relapsed or refractory multiple myeloma (BMA117159)	(Trudel et al., 2018; Trudel, et al., 2019)
Lorvotuzumab Mertansine (IMGN901)	CD-56	DM1	Cleavable disulfide linker	Phase I	NCT00346255	Relapsed and/or Refractory CD-56-positive multiple myeloma	(Ailawadhi et al., 2019)
16. Osteosarcoma
Glembatumumab vedotin (CDX-011)	Glycoprotein non-metastatic B Fully human IgG2 monoclonal antibody	MMAE		Phase II	AOST1521 NCT02487979	Recurrent osteosarcoma	(Kopp et al., 2019)
17. Leukemia
Camidanlumab tesirine	CD25 Humanized antibody	PBD dimer (SG3199)	Cleavable Cathepsin-valine-alanine linker	Phase I	NCT02588092 Therapeutics SA	Acute myeloid leukemia or acute lymphoblastic leukemia	(Goldberg et al., 2020)
Vadastuximab talirine (SGN-CD33A)	CD33 Monoclonal antibody	PBD dimer	Cleavable MC-VC linker	Phase I	NCT01902329 Genetics, Inc.	CD33-positive acute myeloid leukemia	(Stein et al., 2018)
Azacitidine and Gemtuzumab ozogamicin (GO)	CD33 Humanized IgG4 antibody	Calicheamicin		Phase I/II	NCT00766116 Celgene, Inc.	Relapsed acute myeloid leukemia	(Medeiros et al., 2018)
18. Glioma
AMG 595	EGFRvIII Fully human monoclonal antibody	DM1 3–4		Phase I	NCT01475006 Amgen Inc.	Recurrent malignant glioma expressing EGFRvIII	(Rosenthal et al., 2019)
Depatuxizumab mafodotin (ABT-414)	EGFR monoclonal antibody	MMAF	Non-cleavable MC linker	Phase I	NCT01800695 AbbVie	EGFR-amplified recurrent glioblastoma	(van den Bent et al., 2017)
ABT-414	EGFR Humanized recombinant IgG1κ monoclonal antibody	MMAF	Non-cleavable MC linker	Phase I	NCT02573324 NCT02343406 AbbVie	Glioblastoma	(Reardon et al., 2017)