Table 1 |.
ADCs currently approved by the US FDA
| ADC | Target antigen | mAb isotype | Linker type | Payload | Payload class | Payload action | DAR | Disease indication (year of approval) |
|---|---|---|---|---|---|---|---|---|
| Gemtuzumab ozogamicin | CD33 | IgG4 | Cleavable | Ozogamicin | Calicheamicin | DNA cleavage | 2–3 | CD33+ R/R AML (2000)a |
| Brentuximab vedotin | CD30 | IgG1 | Cleavable | MMAE | Auristatin | Microtubule inhibitor | 4 | R/R sALCL or cHL (2011) R/R pcALCL or CD30+ MF (2017) cHL, sALCL or CD30+ PTCL (2018)b |
| Ado-trastuzumab emtansine (T-DM1) | HER2 | IgG1 | Non-cleavable | DM1 | Maytansinoid | Microtubule inhibitor | 3.5 (mean) | Advanced-stage HER2+ breast cancer previously treated with trastuzumab and a taxane (2013); early stage HER2+ breast cancer in patients with residual disease after neoadjuvant trastuzumab-taxane- based treatment (2019) |
| Inotuzumab ozogamicin | CD22 | IgG4 | Cleavable | Ozogamicin | Calicheamicin | DNA cleavage | 5–7 | R/R B-ALL (2017) |
| Fam-trastuzumab deruxtecan-nxki (T-DXd) | HER2 | IgG1 | Cleavable | DXd | Camptothecin | TOPO1 inhibitor | 8 | Advanced-stage HER2+ breast cancer after two or more anti-HER2-based regimens (2019) |
| Polatuzumab vedotin-piiq | CD79b | IgG1 | Cleavable | MMAE | Auristatin | Microtubule inhibitor | 3.5 (mean) | R/R DLBCL (2019)c |
| Sacituzumab govitecan-hziy | TROP2 | IgG1 | Cleavable | SN-38 (active metabolite of irinotecan) | Camptothecin | TOPO1 inhibitor | 8 | Advanced-stage, triple-negative breast cancer in the third-line setting or beyond (2020) |
| Enfortumab vedotin-ejfv | Nectin 4 | IgG1 | Cleavable | MMAE | Auristatin | Microtubule inhibitor | 4 | Advanced-stage urothelial carcinoma, following progression on a PD-l or PD-Ll inhibitor and platinum-containing chemotherapy (2020) |
| Belantamab mafodotin-blmf | BCMA | IgG1 | Non-cleavable | MMAF | Auristatin | Microtubule inhibitor | Unknown | R/R multiple myeloma in the fifth-line setting or beyond (2020) |
ADC, antibody–drug conjugate; AML, acute myeloid leukaemia; B-ALL, B cell acute lymphoblastic leukaemia; BCMA, B cell maturation antigen; cHL, classical Hodgkin lymphoma; DAR, drug-to-antibody ratio; DLBCL, diffuse large B cell lymphoma; mAb, monoclonal antibody; MF, mycosis fungoides; MMAE, monomethyl auristatin E; MMAF, monomethyl auristatin F; pcALCL, primary cutaneous anaplastic large cell lymphoma; PTCL, peripheral T cell lymphoma; R/R, relapsed and/or refractory; sALCL, systemic anaplastic large cell lymphoma; TOPO1, topoisomerase I; TROP2, tumour-associated calcium signal transducer 2.
As a single agent or in combination with daunorubicin and cytarabine. Gemtuzumab ozogamicin was withdrawn from the market in 2010 and re-approved in 2017 for newly diagnosed or R/R CD33-positive AML.
In combination with cyclophosphamide, doxorubicin and prednisone for newly diagnosed sALCL or CD30+ PTCL and in combination with doxorubicin, vinblastine and dacarbazine for newly diagnosed cHL.
In combination with bendamustine and rituximab.