Table 2 Clinical landscape of unconventional ADC payloads
From: Payload diversification: a key step in the development of antibody–drug conjugates
ADC description | Last known clinical development (starting–ending date) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
Payload mechanism | Payload name | ADC name | Antibody (or vector) name | Target | Phase I | Phase I/II | Phase II | Phase III | Indication | Sponsor | NCT number |
Oncology | |||||||||||
Topoisomerase II inhibitors | Doxorubicin | SGN-15 (BMS-182248) | BR-96 | Lewis-Y | 1999–2005 (DISCONTINUED) | Le-Y expressing epithelial tumors, Hormone refractory prostate carcinoma, mBC, NSCLC | Seattle Genetics | NCT00086333, NCT00051571, NCT00031187, NCT00051584, NCT00028483 | |||
IMMU-110 (hLL1-DOX) | Milatuzumab | CD74 | July 2010–July 2013 | multiple myeloma | Immunomedics (Gilead Science) | NCT01101594 | |||||
PNU-159682 | NBE-002 | ROR1 | June 2020 | TNBC, advanced solid tumor, advanced cancer | NBE therapeutics (Boehringer Ingelheim) | NCT04441099 | |||||
SOT102 | CLDN18.2 | April 2022 | Gastric and pancreatic cancer | SOTIO | NCT05525286 | ||||||
RNApolII inhibitors | alpha-amanitin | HDP-101 | J22.9-ISY | BCMA (CD-269) | May 2021 | Multiple myeloma | Heidelberg Pharma | NCT04879043 | |||
Bcl-xL inhibitors | Clezutoclax | ABBV-155 (mirzotamab clezutoclax) | mirzotamab | B7-H3 (CD276) | July 2018 | Advanced solid tumors | AbbVie | NCT03595059 | |||
DHFR inhibitors | Methotrexate | N/A | KS1/4 | 1990 | NSCLC | 105 | |||||
TK inhibitors | Genistein | B43 genistein | B43 | CD19 | March 2000 (DISCONTINUED) | ALL and NHL | Parker Hughes Cancer Center | NCT00004858 | |||
Immune stimulants | TLR7/8 agonist | NJH395 | Unknown | HER2 (ErbB2) | December 2018–2021 (COMPLETED) | Non-Brest HER2 + advanced malignancies | Novartis Pharmaceuticals | NCT03696771 | |||
BDC-1001 | Trastuzumab (biosimilar) | HER2 (ErbB2) | February 2020 | Advanced and HER2-expressing solid tumors | Bolt Biotherapeutics | NCT04278144 | |||||
TLR8 agonist (zuvotolimod) | SBT6050 | Pertuzumab | HER2 (ErbB2) | October 2021 (DISCONTINUED) | HER2-positive tumors | Silverback Therapeutics | NCT05091528, NCT04460456 | ||||
STING agonist (TAK-676) | TAK-500 | CCR2 antibody | CCR2 | October 2021 | advanced or metastatic solid tumors | Takeda | NCT05070247, 188 | ||||
Beyond oncology | |||||||||||
Glucocorticoids | Glucocorticoid receptor modulator | ABBV-3373 | adalimumab (Humira®) | TNF-a | March 2019–Aug 2020 (COMPLETED) | Rheumatoid Arthritis | AbbVie | NCT03823391 | |||
ABBV-154 | n.d | TNF-a | May 2021 | Rheumatoid Arthritis, Severely active Crohn's disease and Polymyalgia Rheumatica | AbbVie | NCT04888585, NCT05068284, NCT04972968 | |||||
RNApolII inhibitors | dmDNA31 | DSTA4637S (Anti-S. aureus TAC, RG-7861) | Human THIOMAB™ anti-S. aureus | Staphylococcus aureus | May 2017–Jan. 2020 (COMPLETED) | Bacteremia | Genentech, Inc | NCT03162250 | |||