Background
Target
Antibody
Linker
Payload
Established targets with approved ADCs
Target | Payload | Linker | DAR | Indications | |
---|---|---|---|---|---|
Trastuzumab emtansine (T-DM1) | HER2 | Maytansine (microtubule inhibitor) | Non-cleavable thioether linker | 3.5 | HER2-positive mBC pretreated with trastuzumab and a taxane; HER2-positive early BC with residual disease after neoadjuvant trastuzumab and taxanes |
Trastuzumab deruxtecan (T-DXd) | HER2 | Deruxtecan (topoisomerase inhibitor) | Protease-cleavable linker | 8 | HER2-positive mBC progressing to two or more prior anti-HER2-based regimens in the metastatic setting |
Enfortumab vedotin (EV) | Nectin-4 | Monomethyl auristatin E (microtubule inhibitor) | Protease-cleavable linker | 3.8 | Locally advanced/metastatic UC previously treated with a PD-(L)1 and a platinum-based chemotherapy in the (neo)adjuvant or metastatic setting |
Sacituzumab govitecan (SG) | Trop-2 | SN-38 (topoisomerase inhibitor) | Hydrolysable linker | 7.5 | Triple-negative mBC (who have received at least two prior therapies for metastatic disease) |
HER2
Trastuzumab emtansine
Trastuzumab deruxtecan
SYD985
NECTIN4
Enfortumab vedotin
TROP-2
Sacituzumab govitecan
HR+/HER2− BC
Urothelial carcinoma
Selecting patients for Trop-2 expression: the TROPiCS-03 study
Promising new targets under investigation
LIV1
Ladiratuzumab vedotin (SGN-LIV1A)
Antibody–drug conjugate | Patload | Trial | Phase | Population | Treatment arm(S) | Biomarker |
---|---|---|---|---|---|---|
CEACAM5 | ||||||
SAR408701 | DM4 (tubulin inhibitor) | NCT02187848 | I/II | Advanced solid tumors | SAR408701 monotherapy | No |
NCT04524689 (CARMEN-LC05) | II | Non-squamous mNSCLC (wild type for EGFR, ALK/ROS1, BRAF) | SAR408701 + pembrolizumab; pembrolizumab monotherapy | Yes | ||
NCT04394624 (CARMEN-LC04) | II | Non-squamous mNSCLC | SAR408701 + ramucirumab | yes | ||
NCT04154956 (CARMEN-LC04) | III | Non-squamous mNSCLC | SAR408701 monotherapy; docetaxel | Yes | ||
c-MET | ||||||
Telisotuzumab vedotin (teliso-V) | MMAE (tubulin inhibitor) | NCT02099058 | I | Advanced solid tumors (mNSCLC in dose expansion) | Teliso-V monotherapy Teliso-V + erlotinib (NSCLC) Teliso-V + nivolumab (NSCLC) Teliso-V + osimertinib (NSCLC) | Yes (dose expansion) |
NCT03539536 | II | mNSCLC | Telisotuzumab vedotin monotherapy | Yes | ||
TR1801-ADC | Pyrrolobenzodiazepine (DNA-crosslinking agent) | NCT03859752 | I | Advanced solid tumors | TR1801-ADC monotherapy | Yes |
SHR-A1403 | Novel microtubule inhibitor | NCT03856541 | I | Advanced solid tumors | SHR-A1403 monotherapy | No |
FOLATE RECEPTOR ALPHA | ||||||
Mirvetuximab soravtansine (IMGN853) | DM4 (tubulin inhibitor) | NCT02606305 | I/II | Advanced OC, fallopian tube, primary peritoneal cancer | IMGN853 + bevacizumab; IMGN853 + carboplatin; IMGN853 + pegylated liposomal doxorubicin; IMGN853 + pembrolizumab; IMGN853 + bevacizumab + carboplatin | Yes |
NCT03832361 | II | mEC | IMGN853 monotherapy | Yes | ||
NCT02996825 | I | Recurrent OC, primary peritoneal, fallopian tube, mEC, mTNBC | IMGN853 + gemcitabine | Yes | ||
NCT03552471 | I | Advanced OC, fallopian tube, primary peritoneal cancer or mEC | IMGN853 + rucaparib | Yes | ||
NCT03835819 | II | mEC | IMGN853 + pembrolizumab | Yes | ||
NCT04606914 | II | Advance-stage OC, fallopian tube, primary peritoneal cancer (neoadjuvant setting) | IMGN853 + carboplatin | Yes | ||
NCT04274426 (MIROVA) | II | Recurrent OC, fallopian tube, primary peritoneal cancer | IMGN853 + carboplatin; Platinum-based chemotherapy | Yes | ||
NCT04209855 (MIRASOL) | III | Advanced OC, fallopian tube, primary peritoneal cancer | IMGN853; Chemotherapy of investigator’s choice (paclitaxel or topotecan or pegylated liposomal doxorubicin) | Yes | ||
NCT04296890 (SORAYA) | III | mOC, fallopian tube, primary peritoneal cancer | IMGN853 monotherapy | Yes | ||
STRO-002 | Hemiasterlin (tubulin inhibitor) | NCT03748186 | I | Advanced OC, fallopian tube, primary peritoneal cancer, mEC | STRO-002 monotherapy | No |
MORAb-202 | Eribulin (tubulin inhibitor) | NCT03386942 | I | Advanced solid tumors | MORAb-202 monotherapy | Yes (only for selected subtypes) |
NCT04300556 | I/II | mOC, fallopian tube, primary peritoneal cancer, mTNBC, mEC, NSCLC adenocarcinoma | MORAb-202 monotherapy | Yes (dose expansion) | ||
HER3 | ||||||
Patritumab deruxtecan (U3-1402) | Deruxtecan (TOP1 inhibitor) | NCT02980341 | I/II | mBC | Patritumab deruxtecan monotherapy | Yes |
NCT03260491 | I | mNSCLC | Patritumab deruxtecan monotherapy | No | ||
NCT04479436 | II | mCRC | Patritumab deruxtecan monotherapy | 2 cohorts (IHC 2+/3+; 1+/0) | ||
NCT04610528 | Early phase I | HR+/HER2- eBC (treatment-naïve patients) | Patritumab deruxtecan monotherapy | 4 cohorts | ||
NCT04619004 (HERTHENA-Lung01) | II | EGFR-mutated mNSCLC | Patritumab deruxtecan monotherapy | No | ||
LIV-1 | ||||||
Ladiratuzumab vedotin (SGN-LIV1A) | MMAE (tubulin inhibitor) | NCT01969643 | I | mBC | SGN-LIV1A monotherapy; SGN-LIV1A + trastuzumab (part B) | No |
NCT03310957 | Ib/II | mTNBC (first-line setting) | SGN-LIV1A + pembrolizumab | No | ||
NCT04032704 | II | Advanced SCLC, NSCLC, HNSCC, ESCC, GC, GEJC, prostate cancer, melanoma | SGN-LIV1A monotherapy | No | ||
NCT03424005 (Morpheus-TNBC)* | I/II | mTNBC | SGN-LIV1A + atezolizumab | No | ||
NCT01042379 (I-SPY2)* | I | Triple-negative eBC (neoadjuvant setting) | SGN-LIV1A monotherapy | No | ||
MESOTHELIN | ||||||
Anetumab ravtansine | DM4 (tubulin inhibitor) | NCT03126630 | I/II | MPM | Anetumab ravtansine + pembrolizumab; Pembrolizumab monotherapy | Yes |
NCT03102320 | I | Advanced solid tumors | Anetumab ravtansine monotherapy; Anetumab ravtansine + gemcitabine; Anetumab ravtansine + cisplatin | Yes | ||
NCT03587311 | I/II | Advanced OC, fallopian tube, or primary peritoneal cancer | Anetumab ravtansine + bevacizumab; Paclitaxel + bevacizumab | Yes (only for part 2) | ||
NCT03816358 | I/II | Pancreatic adenocarcinoma | Anetumab ravtansine + nivolumab; Anetumab ravtansine + nivolumab + ipilimumab; Anetumab ravtansine + nivolumab + gemcitabine | Yes | ||
RC88 | MMAE (tubulin inhibitor) | NCT04175847 | I | Advanced solid tumors | RC88 monotherapy | Yes |
BMS-986148 | Tubulysin (tubulin inhibitor) | NCT02341625 | I/II | MPM, NSCLC, OC, GC, pancreatic cancer | BMS-986148 monotherapy; BMS-986148 + nivolumab | Yes (dose expansion) |
TISSUE FACTOR | ||||||
Tisotumab vedotin | MMAE (tubulin inhibitor) | NCT03485209 (InnovaTV 207) | II | mCRC, pancreatic cancer, squamous NSCLC, HNSCC | Tisotumab vedotin monotherapy | No |
NCT03438396 | II | mCC | Tisotumab vedotin monotherapy | No | ||
NCT03657043 (InnovaTV 208) | II | Advanced OC, fallopian tube, peritoneal cancer | Tisotumab vedotin monotherapy | No | ||
NCT03786081 | I/II | mCC | Tisotumab vedotin monotherapy Tisotumab vedotin + carboplatin Tisotumab vedotin + pembrolizumab Tisotumab vedotin + bevacizumab | No |