Table 3.
Antibody–drug conjugates in clinical development.
| Payload | Target Antigen | Antibody–Drug Conjugates | Antibody | Linker | Lead Indication | Trial Phase | ClinicalTrials.gov Identifier | Reference |
|---|---|---|---|---|---|---|---|---|
| AGD-0182 | FLT3 | AGS62P1 (ASP1235) |
Human IgG1 | Non-cleavable linker | Acute myeloid leukaemia (AML) | I | NCT02864290 | [101] |
| Amberstatin-269 | FLT3 | AGS-62P1 | Humanized IgG1 | Cleavable linker | AML | I | NCT02864290 | |
| Auristatin-0101 | ErbB2 | PF-06804103 | Humanized IgG1 | Protease-cleavable linker | Advanced solid tumors | I | NCT03284723 | [102] |
| PTK7 | Cofetuzumab pelidotin PF-7020 |
Humanized IgG1 | Cleavable maleimidoca- proyl -valine-citrulline (mc-vc) PABC linker | Non-small-cell lung cancer (NSCLC), advanced solid tumors | I |
NCT04189614 NCT02222922 |
[103] | |
| Auristatin derivative | IGF-1R | W0101 | Humanized IgG1 | Non-cleavable maleimidoca- proyl (mc) linker |
Advanced solid tumors | I/II | NCT0331638 | [104] |
| Auristatin | ErbB2 | ZW49 | Biparatopic IgG | Protease-cleavable linker |
ErbB2-expressing cancers | I | NCT03821233 | [105] |
| Auristatin F | 5T4 | ASN-004 | Humanized scFvFc antibody | Non-cleavable linker | Advanced solid tumors | I | NCT04410224 | |
| Auristatin F-HPA (DolaLock) | SLC34A2 (NaPi2b) |
XMT-1592 | Humanized IgG1 | Protease-cleavable linker |
NSCLC, ovarian cancer | I/II | NCT04396340 | |
| SLC34A2 (NaPi2b) |
XMT-1536 | Humanized IgG1 | Protease-cleavable linker |
NSCLC, ovarian cancer | I | NCT03319628 | [106] | |
| Batansine | ErbB2 | BAT8001 | Humanized IgG1 | Non-cleavable linker | Metastatic breast cancer | I |
NCT04189211 NCT04151329 |
[107] |
| TROP2 | BAT8003 | IgG1 | Non-cleavable linker | Advanced epithelial cancer | I | NCT03884517 | [108] | |
| Dolastatin analogue | AG7 | ABGn-107 | Humanized IgG | Cleavable linker | Gastric, colorectal, pancreatic, or biliary cancer |
I | NCT02908451 | [109] |
| DM1 | CD30 | F0002-ADC | Chimeric IgG1κ | Non-cleavable SMCC linker |
Hematologic malignancies | I | NCT03894150 | [110] |
| CD37 | Naratuximab emtansine (IMGN-529, DEBIO 1562) |
Humanized IgG1 | Non-cleavable SMCC linker |
Non-Hodgkin’s lymphoma (NHL) | I | NCT01534715 | [111] | |
| CD56 | Lorvotuzumab Mertansine (LM, IMGN-901) |
Humanized IgG1 | Disulfide linker | Multiple myeloma, small-cell lung cancer (SCLC), Merkel cell, ovarian cancer | I/II | NCT02452554 | [112,113,114] | |
| EGFR | AVID100 | IgG | Non-cleavable SMCC linker |
Advanced epithelial carcinomas |
I/II | NCT03094169 | [115] | |
| ErbB2 | B003 | Humanized IgG1 | Thioether linker | Metastatic breast cancer | I | NCT03953833 | ||
| DM4 | CD205 | MEN1309 (OBT076) |
Humanized IgG1 | Cleavable SPDB linker | Solid tumors, breast cancer, NHL | I | NCT04064359 | [116] |
| CD138 | Indatuximab ravtansine (BT062) | Chimeric IgG4 |
Cleavable disulfide linker |
Multiple myeloma | I/IIa | NCT01638936 | [117,118] | |
| CD166 | CX-2009 | Probody | Cleavable SPDB linker | Solid tumors | I/II | NCT03149549 | [119] | |
| CEACAM5 | SAR408701 | Humanized IgG1 |
Cleavable linker | Solid tumors | III | NCT04154956 | [120] | |
| Folate receptor α (FRα) | Mirvetuximab soravtansine (IMGN-853) |
Humanized IgG1 | Cleavable SPDB linker | NSCLC, ovarian cancer | I/II/ III |
NCT01609556 NCT02631876 NCT03552471 NCT02496890 NCT03832361 |
[121] | |
| Mesothelin (MSLN) |
Anetumab ravtansine (BAY 94-9343) | Human IgG1 | Cleavable SPDB linker | Mesothelioma, Solid tumors |
II |
NCT03832361 NCT04296890 NCT03552471 NCT03023722 NCT04209855 NCT02996825 |
[122,123] | |
| DUBA (Seco-duocarmycin-hydroxy-benzamide-azainodole) |
ErbB2 | Trastuzumab duocarmazine (SYD985) | Humanized IgG1 | Cleavable linker | Endometrial carcinoma, metastatic breast cancer, |
II/III |
NCT04205630 NCT03262935 |
[39] |
| B7-H3 | MGC018 | Humanized IgG1 | Cleavable valine-citrulline linker | Advanced solid tumors | I/II | NCT03729596 | [124] | |
| Duocarmycin analogue | 5T4 | SYD1875 | Humanized IgG1 |
Cleavable valine-citrulline-seco linker | Advanced solid tumors | I/II | NCT04202705 | |
| Dxd (DX-8951) |
B7-H3 | DS-7300a | Humanized IgG1 |
Cleavable linker | Advanced solid tumors | I | NCT04145622 | |
| ErbB3 | U3-1402 | Humanized IgG1 | Cleavable linker | NSCLC, breast cancer, colorectal cancer | I/II |
NCT03260491, NCT02980341, NCT04479436 |
[125] | |
| GPR20 | DS-6157a | Unknown | Cleavable Gly-Gly-Phe-Gly (GGFG) linker | Advanced gastrointestinal stromal tumor | I | NCT04276415 | [126] | |
| TROP-2 | DS-1062a | Humanized IgG1 | Cleavable linker | NSCLC, Advanced solid tumors | I |
NCT04526691 NCT03401385 |
[127] | |
| Eribulin | FRα | MORAb-202 | Humanized IgG1 | Cleavable mal-PEG2-vc-PABC |
Solid tumors | I | NCT03386942 | [128] |
| IGN (Indolino-benzodiazepine dimer) | CD123 | IMGN 632 Orphan drug designation |
Humanized IgG1 |
Cleavable peptide linker | AML, Acute lymphoblastic leukaemia (ALL) | I/II | NCT03386513 | [129] |
| MMAE | AXL | Enapotamab vedotin (HuMax-AXL-ADC) |
Human IgG1 | Cleavable mc-vc linker | Solid tumors | I/II | NCT02988817 | [130] |
| AXL | BA3011 (CAB-AXL-ADC) |
Humanized IgG1 |
Cleavable linker | Advanced solid tumors | I/II | NCT03425279 | [131] | |
| CD71 | CX-2029 | Probody | Protease-cleavable mc-vc-PAB linker |
DLBCL, Solid tumors | I/II | NCT03543813 | [132] | |
| CD228 | SGN-CD228A | Humanized IgG1 | Protease-cleavable linker | Advanced solid tumors | I | NCT04042480 | [133] | |
| C-Met | ABBV-399 Telisotuzumab vedotin |
Humanized IgG1 |
Cleavable mc-vc linker | Non-small-cell lung cancer | II | NCT03539536 | [134] | |
| ErbB2 | Disitimab vedotin (RC48-ADC) |
Humanized IgG1 | Protease-cleavable linker | Metastatic breast cancer with low ErbB2 expression | III | NCT04400695 | [135,136] | |
| ErbB2 | ALT-P7 | Humanized IgG1 | Unknown | Breast cancer | I | NCT03281824 | [137] | |
| ErbB2 | MRG002 | IgG | Unknown | Breast cancer, gastric cancer | I/II | NCT04492488 | [138] | |
| EGFR | MRG003 | IgG | Unknown | Solid tumors | I | CTR20180310 | ||
| Globo H | OBI-999 Orphan drug approval from the FDA |
Humanized IgG1 | Cleavable thiobridge linker |
Advanced solid tumors | I/II | NCT04084366 | [139] | |
| Integrin beta-6 | SGN-B6A | IgG | Unknown | Advanced solid tumors | I | NCT04389632 | ||
| ROR1 | VLS-101 (UC-961ADC3) |
Humanized IgG1 | Unknown | Advanced breast cancer, NSCLC, haematological malignancies | I | NCT04504916 | [140] | |
| SLC39A6 (LIV-1) |
Ladiratuzumab vedotin (SGN-LIV1A) |
Humanized IgG1 | Cleavable mc-vc linker | NSCLC, head and neck cancer, gastric cancer, breast cancer | I/II |
NCT04032704 NCT03310957 NCT01969643 |
[141] | |
| Tissue factor (TF, CD142) |
Tisotumab vedotin (HuMax-TF-ADC) |
Human IgG1 | Protease-cleavable mc-vc-PAB linker |
Advanced ovarian cancer | II | NCT03657043 | [142] | |
| MMAF | ErbB2 | ARX788 | IgG1 | pAcF linker | ErbB2-expressing cancers | I | NCT03255070 | [143] |
| ErbB2 | FS-1502 (LCB14-0110) |
Humanized IgG1 | Unknown | ErbB2-positive advanced solid tumors | I | NCT03944499 | ||
| MMAF derivative (Duostatin-5) |
ErbB2 | A166 | Humanized IgG1 |
Unknown | ErbB2-expressing tumors | I/II | NCT03602079 | [144] |
| Maytansinoid | CD22 | TRPH-222 | Humanized IgG | Non-cleavable linker | B cell lymphoma | I | NCT03682796 | [145] |
| PBD | BCMA | MEDI2228 | Humanized IgG1 | Cleavable protease linker | Multiple myeloma | I | NCT03489525 | |
| c-MET | TR 1801-ADC (MT-8633) |
Humanized IgG2 | Cleavable Val-Ala linker | c-MET-expressing tumors | I | NCT03859752 | ||
| CD19 | Loncastuximab tesirine (ADCT-402) |
Humanized IgG1 | Cleavable Valine-Ala linker | NHL | III | NCT04384484 | [146] | |
| CD25 | Camidanlumab tesirine (ADCT-301) |
Humanized IgG1 | Cleavable linker | AML, ALL, HL, NHL, solid tumors | I/II |
NCT04052997 NCT03621982 |
[147] | |
| EGFR | ABBV-321 Serclutamab talirine |
IgG | Solid tumors | I | NCT03234712 | [148] | ||
| GCC | TAK-164 | Human IgG | Cleavable peptide linker | Gastrointestinal malignancies | I | NCT03449030 | [149] | |
| SC236 | CD74 | STRO-001 | Human IgG1 | Non-cleavable DBCO linker |
NHL, B cell malignancies | I | NCT03424603 | [150] |
| SC209 | FR α | STRO-002 | Human IgG1 | Cleavable linker | Ovarian and endometrial cancers |
I | NCT03748186 | [151] |
| SG3249 (PBD derivative) |
CD22 | ADCT-602 (Epratuzumab tesirine) |
Humanized IgG1 | Cleavable Val-Ala linker | B cell acute lymphoblastic leukaemia |
I/II | NCT03698552 | |
| SHR152852 | c-MET | SHR-A1403 (HTI-1066) |
Humanized IgG2 | Non-cleavable linker | Advanced solid tumors | I | NCT03856541 | [152] |
| PNU-159682 | ROR1 | NBE-002 | IgG | Unknown | Advanced solid tumors, triple-negative breast cancer | I | NCT04441099 | |
| Belotecan-derived payload | TROP2 | SKB-264 | IgG | Unknown | Advanced solid tumors | I/II | NCT04152499 | |
| TLR7/TLR8 agonist | ErbB2 | BDC-1001 | Humanized IgG1 | Unknown | ErbB2-positive advanced solid tumors | I | NCT04278144 | |
| TLR8 agonist | ErbB2 | SBT6050 | IgG | Unknown | ErbB2-positive advanced solid tumors | I | NCT04460456 | |
| Unknown | ROR2 | BA 3021 (CAB-ROR2-ADC) |
Humanized IgG1 |
Unknown | Advanced solid tumors | I/II | NCT03504488 | |
| Unknown | CD46 | FOR-46 | Humanized IgG1 |
Unknown | Multiple myeloma, prostate cancer | I |
NCT03650491 NCT03575819 |
|
| Unknown | Unknown | ABBV-011 | IgG | Unknown | Small-cell lung cancer | I | NCT0369194 | |
| Unknown | Unknown | ABBV-155 | IgG | Unknown | Solid tumors | I | NCT03595059 | |
| Unknown | ErbB2 | DP303c | IgG | Unknown | ErbB2-positive advanced solid tumors | I | NCT04146610 | |
| Unknown | BCMA | CC-99712 (BCMA-ADC) |
IgG | Unknown | Multiple myeloma | I | NCT04036461 | |
| Unknown | ErbB2 | GQ1001 | IgG | Unknown | ErbB2-positive advanced solid tumors | I | NCT04450732 | |
| Unknown | ErbB2 | BB-1701 | IgG | Unknown | ErbB2-positive advanced solid tumors | I | NCT04257110 | |
| Unknown | ErbB2 | SHR-A1811 | IgG | Unknown | ErbB2-positive advanced solid tumors | I |
NCT04513223 NCT04446260 |
|
| Unknown | CCR7 | JBH492 | IgG | Unknown | CLL, NHL | I | NCT04240704 |