Table 1.
Approved ADCs with their oncological indications and their characteristics.
| ADC | Manufacturer | Year of initial FDA approval | Indications | Target | Antibody | Payload | Linker | DAR | Common adverse events (>10%) |
|---|---|---|---|---|---|---|---|---|---|
| Gemtuzumab ozogamicin (Mylotarg®, CMA-676) | Pfizer/Wyeth | 2000, withdrawn 2010, reapproved 2017 | Newly diagnosed (de novo) CD33+ AML in adults (as a monotherapy or combined with chemotherapy) and pediatric patients 1 month and older (combined with chemotherapy) and relapsed/refractory CD33+ AML in adults and pediatric patients ⩾2 years of age | CD33 | Humanized IgG4 | Calicheamicin derivative | Acid-labile hydrazone linker | ~2–3 | Infection, hemorrhage, thrombocytopenia, hypophosphatemia, hypokalemia, hyponatremia, nausea, vomiting, elevated ALP, elevated aminotransferase, fatigue, febrile neutropenia, constipation, abdominal pain, pyrexia, mucositis |
| Brentuximab vedotin (Adcetris®, SGN-35) | Seattle Genetics, Millennium/Takeda | 2011 | Previously untreated stage III/IV cHL (combined with chemotherapy), cHL at high risk of relapse or progression as post-auto-HSCT consolidation, cHL after failure of auto-HSCT or after failure of ⩾2 prior chemotherapy regimens, previously untreated sALCL or other CD30+ peripheral T-cell lymphomas (combined with chemotherapy), relapsed sALCL, relapsed peripheral cutaneous ALCL or CD30+ MF | CD30 | Chimeric IgG1 | MMAE | Protease-cleavable dipeptide (Val–Cit) linker | ~4 | Neutropenia, peripheral sensory neuropathy, fatigue, upper respiratory tract infection, nausea, diarrhea, anemia, thrombocytopenia, pyrexia, rash, abdominal pain, vomiting, arthralgia, myalgia, pruritus, peripheral motor neuropathy, headache, constipation, dizziness, lymphadenopathy, dyspnea, back pain, anxiety |
| Ado-trastuzumab emtansine (T-DM1, Kadcyla®) | Genentech, Roche | 2013 | Unresectable locally advanced or metastatic HER2+ breast cancer, previously treated with trastuzumab and a taxane, adjuvant treatment for HER2+ early breast cancer with residual invasive disease after neoadjuvant taxane and trastuzumab | HER2/ERB2 | Humanized IgG1 | DM1 | Thioether (non-cleavable) linker | 3.5 | Nausea, constipation, diarrhea, vomiting, abdominal pain, dry mouth, stomatitis, headache, peripheral neuropathy, dizziness, epistaxis, cough, dyspnea, fatigue, musculoskeletal pain, arthralgia, myalgia, pyrexia, thrombocytopenia, anemia, increased aminotransferases, insomnia, rash, hypokalemia |
| Inotuzumab ozogamicin (Besponsa®, CMC-544) | Pfizer/Wyeth | 2017 | Relapsed or refractory CD22+ B-cell precursor ALL in adults | CD22 | Humanized IgG4 | Calicheamicin derivative | Acid-labile hydrazone linker | ~4 | Thrombocytopenia, neutropenia, infection, anemia, leukopenia, nausea, fatigue, hemorrhage, pyrexia, elevated transaminases, febrile neutropenia, elevated gamma-glutamyl transferase, lymphopenia, headache, abdominal pain, diarrhea, constipation, vomiting, stomatitis, elevated ALP |
| Polatuzumab vedotin-piiq (Polivy®, DCDS4501A, RG7596) | Genentech, Roche | 2019 | Relapsed or refractory diffuse large B-cell lymphoma (combined with bendamustine and rituximab) in adult patients after ⩾2 prior therapies | CD79b | Humanized IgG1 | MMAE | Protease-cleavable dipeptide (Val–Cit) linker | 3.5 | Neutropenia, thrombocytopenia, anemia, leukopenia, lymphopenia, febrile neutropenia, peripheral neuropathy, dizziness, diarrhea, vomiting, infusion-related reactions, pyrexia, decreased appetite, fatigue, pneumonia, upper respiratory tract infection, decreased weight, hypokalemia, hypoalbuminemia, hypocalcemia |
| Enfortumab vedotin (Padcev®, AGS-22M6E, AGS-22CE) | Astellas/Seattle Genetics | 2019 | Locally advanced or metastatic urothelial cancer in adult patients who had received prior treatment with a PD-1/L1 inhibitor and platinum-based chemotherapy in neoadjuvant/adjuvant setting | Nectin 4 | Fully human IgG1 | MMAE | Protease-cleavable dipeptide (Val–Cit) linker | ~3.8 | Peripheral neuropathy, dysgeusia, fatigue, decreased appetite, rash, alopecia, dry skin, pruritus, dry eye, nausea, vomiting, constipation |
| Fam-trastuzumab deruxtecan-nxki (Enhertu®, DS-8201a, T-DXd) | AstraZeneca/Daiichi Sankyo | 2019 | Unresectable or metastatic HER2+ breast cancer in adult patients who have previously received ⩾2 HER2 blockade regimens in the metastatic setting | HER2/ERB2 | Humanized IgG1 | DXd (exatecan derivative) | Protease-cleavable tetrapeptide (Gly–Gly–Phe–Gly) linker | 7–8 | Nausea, vomiting, constipation, diarrhea, abdominal pain, stomatitis, dyspepsia, fatigue, alopecia, rash, decreased appetite, hypokalemia, anemia, neutropenia, leukopenia, thrombocytopenia, cough, dyspnea, epistaxis, headache, dizziness, upper respiratory tract infection, dry eye |
| Sacituzumab govitecan-hziy (Trodelvy® IMMU-132, HRS7-SN38) | Immunomedics | 2020 | Unresectable locally advanced or metastatic triple negative (HR−/HER2−) breast cancer after at least 2 prior chemotherapies | Trop-2 | Humanized IgG1 | SN-38 | CL2A linker | 7.6 | Nausea, diarrhea, neutropenia, fatigue, anemia, vomiting, constipation, alopecia, rash, headache, respiratory tract infection, decreased appetite, urinary tract infection, hyperglycemia, arthralgia, dyspnea, dizziness, neuropathy, back pain, edema, thrombocytopenia, hypomagnesemia, hypokalemia, hypophosphatemia, pruritus, mucositis |
ADC, antibody–drug conjugate; ALL, acute lymphoblastic lymphoma; ALP, alkaline phosphatase; AML, acute myeloid leukemia; cHL, classic Hodgkin’s lymphoma; DAR, drug-to-antibody ratio; DM1, maytansine 1 derivative; FDA, US Food and Drug Administration; HER2, human epidermal growth factor receptor 2; HR: hormonal receptor; HSCT, hematopoietic stem cell transplant; MF, mycosis fungoides; MMAE, monomethyl auristatin E; sALCL, systemic anaplastic large cell lymphoma; Val–Cit, valine–citrulline.