From: Payload diversification: a key step in the development of antibody–drug conjugates
Payload name | ADC name | Antibody | Antibody target | linker | Conjugation site | DAR | Development status | Indication | Last publication date or clinical trial status | Reference |
---|---|---|---|---|---|---|---|---|---|---|
Dxd | DsS8201a, trastuzumab deruxtecan, Enhertu | trastuzumab | HER2 | mc-GGFG-AM cleavable | cysteine | 8 | FDA approved | unresectable or metastatic HER2 + BC, gastric or gastroesophageal carcinoma | N/A | 48 |
U3-1402, patritumab deruxtecan | patritumab | HER3 | mc-GGFG-AM cleavable | cysteine | 8 | phase II | NSCLC, metastatic colorectal, metastatic BC and BC | Recruiting or active | NCT04479436, NCT03260491, NCT02980341, NCT04619004, NCT04676477, NCT04699630, NCT04610528, NCT0496576 | |
Ds-1062a, datopotamab deruxtecan | datopotamab | TROP2 | mc-GGFG-AM cleavable | cysteine | 4 | phase III | NSCLC, metastatic lung cancer, TNBC, HR + BC, BC | Recruiting or active | NCT02923115, NCT03742102, NCT04526691, NCT04612751, NCT05104866, NCT03401385, NCT04940325, NCT04656652, NCT04484142, NCT05215340 | |
Ds-7300a | B7-H3 antibody | B7-H3 | mc-GGFG-AM cleavable | cysteine | 4 | phase I/II | Advanced solid malignant tumors | Recruiting or active | NCT04145622 | |
Ds-6157a | GPR20 antibody | GPR20 | mc-GGFG-AM cleavable | cysteine | 8 | Phase I | GIST | Recruiting or active | NCT04276415 | |
SN-38 | IMMU-132, sacituzumab govitecan, Trodelvy TM | sacituzumab (hRS7) | TROP2 | Cleavable CL2A (hydrolyzable) | cysteine | 7.6 | FDA approved | HER + /HER-Metastatic BC (mTNBC) | N/A | 49 |
IMMU-130 | labetuzumab (hMN-14) | CEACAM5 | Cleavable CL2A (pH-sensitive) | cysteine | 7.6 | Phase II (withdrawn) | Solid tumors (metastatic colorectal; colon cancer; rectal cancer) | 2020 (Phase II withdrawal) | NCT01270698, NCT01605318, NCT01915472 | |
IMMU-140 | IMMU–112 (hL243) | HLA-DR | Cleavable CL2A (pH-sensitive) | cysteine | 6.1 | late preclinical | ALL, CLL, MM, AML, DLBCL, HL and melanoma | 2018 | 87 | |
Epratuzumab (hLL2) | CD22 | Cleavable CL2A (pH-sensitive) or CL2E (cathepsin cleavable) | cysteine | 6 | preclinical | B cell malignancy, Lymphoma and leukemia | 2012 | 88 | ||
Veltuzumab | CD20 | Cleavable CL2A (pH-sensitive) or CL2E (cathepsin cleavable) | cysteine | 6 | preclinical | B cell malignancy | 2012 | 88 | ||
Milatuzumab | CD74 | Cleavable CL2A (pH-sensitive) or CL2E (cathepsin cleavable) | cysteine | 6.5–6.6 | Preclinical | solid cancers (and lymphoma) | 2013 | 89 | ||
Trastuzumab | HER2 | ester bond or carbonate cleavable (± PEG4) | Cysteine | 3.2–3.7 | preclinical | ovarian | 2015 | 90 | ||
A7R | IL-7R | Carbamate bond + PEG12 | Cysteine | 4 to 6 | late preclinical | IL-7R + Lymphoid malignancies, autoimmune diseases, metastatic solid tumors | 2018 | 93 | ||
rituximab | CD20 | Carbamate or ester cleavable + PEG27 | cysteine | 7 | preclinical | Lymphoma | 2013 | 91 | ||
B8-4 | EpCam | Carbamate or ester cleavable + PEG27 | cysteine | 8.5 | preclinical | Pancreatic cancer | 2013 | 91 | ||
35–4 | Collagen-4 | Carbamate or ester cleavable + PEG27 | cysteine | 7.5 | preclinical | hypovascular stroma-rich tumor (pancreatic) | 2013 | 91 | ||
AZ'0132 (exatecan derivative) | AZD8205 | B7-H4 antibody | n.d | n.d | n.d | 8 | Phase I/Phase II | breast, ovarian and endometrial cancers and cholangiocarcinoma | 2021 | NCT05123482, 69 |
KL610023 (belotecan derivative) | SKB-264 | n.d | TROP2 | n.d | n.d | 7.4 | Phase I/II | ovarian epithelial and breast cancer, gastric and urothelial carcinoma, NSCLC, SCLC | Recruiting or active | NCT04152499 |
Exatecan mesylate | Trastuzumab | HER2 | cleavable glucuronide + PSARLink | cysteine | 8 | preclinical | HER2 + solid tumors | 2021 | 36 | |
PRO1184 | Fra antibody | Fra | hydrophilic protease cleavable | cysteine | 8 | late preclinical | NSCLC, ovarian | 2022 | 77 | |
PRO1102 | Trastuzumab | HER2 | hydrophilic protease cleavable | cysteine | 8 | POC | 2022 | 76 | ||
PRO1160 | CD70 antibody | CD70 | hydrophilic protease cleavable | cysteine | 8 | preclinical | 2022 | 78 | ||
7-n-butyl-10-amino-CPT | cAC10 | CD30 | mc-Val-cit-PAB or glucuronide cleavable linkers | cysteine | 4 to 8 | preclinical | hematologic malignancies | 2009 | 94 | |
h1F6 | CD70 | mc-Val-cit-PAB or glucuronide cleavable linkers | cysteine | 4 to 8 | preclinical | hematologic malignancies and renal cell carcinoma | 2009 | 94 | ||
cBR96 | LeY | mc-Val-cit-PAB or glucuronide cleavable linkers | cysteine | 4 to 8 | preclinical | carcinoma | 2009 | 94 | ||
7-n-butyl-9-amino-10, 11-MDO-CPT | cAC10 | CD30 | mc-Val-cit-PAB or glucuronide cleavable linkers | cysteine | 4 to 8 | preclinical | hematologic malignancies | 2009 | 94 | |
h1F6 | CD70 | mc-Val-cit-PAB or glucuronide cleavable linkers | cysteine | 4 to 8 | preclinical | hematologic malignancies and renal cell carcinoma | 2009 | 94 | ||
cBR96 | LeY | mc-Val-cit-PAB or glucuronide cleavable linkers | cysteine | 4 to 8 | preclinical | carcinoma | 2009 | 94 | ||
CPT | trastuzumab | HER2 | Pt–PEG, ester cleavage | cysteine | 2.5–4 | POC | Solid tumors | 2017 | 95 | |
cetuximab | EGFR | Pt–PEG, ester cleavage | cysteine | 2.5–4 | POC | Solid tumors | 2017 | 95 | ||
rituximab | CD20 | Pt–PEG, ester cleavage | cysteine | 2.5–4 | POC | N/A | 2017 | 95 | ||
AMDCPT | SGN-CD30c | cAC10 | CD30 | maleimidopropionyl-PEG7-valine-lysine-glycine | cysteine | 8 | late preclinical | Relapse and refractory lymphoma | 2020 | 97, 98 |
cAC10 | CD30 | val-lysine-glycine tripeptide ± PEG4 or PEG8 | cysteine | 8 | preclinical | lymphoma | 2021 | 96 | ||
other CPT derivative | EGFR or Fra | mc-AAA-AM cleavable ± polyhydroxyl moiety | cysteine | 6.4–7.5 | preclinical | solid tumors | 2019 | 79 |