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Clinical Trial Stage |
ADC name |
Antibody/Linker |
Cytotoxic drugs |
Cancer types |
Antigen targeted |
Phase I |
ASG-22ME |
Hu IgG1/valine-citrulline (V.C) |
MMAE |
Urothelial and other malignant solid tumors |
Nectin-4 |
SAR566658 |
Hz IgG1/DS6 disulfide |
Maytansinoid |
Malignant neoplasm, triplenegative breast cancer |
CA6 |
|
BAY 94-9343 |
H IgG1/disulfide, HuIgG1/SPDB |
Maytansinoid, (DM4) |
Mesothelin-positive solid tumors |
Mesothelin |
|
IMGN388 |
IgG1/disulfide |
Maytansinoid |
Solid tumors |
Integrin αv |
|
BIIB015 |
IgG1/disulfide |
Maytansinoid |
Anti-Cripto, refractory solid tumors |
Cripto-1 |
|
SGN-75 |
Anti D70/dipeptide |
Auristatin |
Renal cell carcinoma |
CD70 |
|
AGS-22M6E |
Anti-Nectin fully human IgG/dipeptide |
Auristatin |
Malignant solid tumors |
Nectin4 |
|
IMGN529 |
K7153A humanized IgG1/ thioether |
Maytansinoid |
B cell malignancies |
CD37 |
|
AMG595 |
Anti-EGFRvIII fully human IgG1/thioether |
Maytansinoid |
Glioblastoma |
EGFRvIII |
|
RG7593/DCDT2980S |
Hz IgG1/valine-citrulline |
MMAE |
NHL |
CD22 |
|
SAR566658 |
Hu IgG1/SPDB |
Maytansine (DM4) |
Solid tumors |
CA6 |
|
Labestuzumab-SN-38 |
HzIgG1/phenylalanine-lysine |
SN38 |
Colorectal cancer |
CD66e/CEACAM5 |
|
AGS-16C3F |
Hu IgG2/maleimidocaproyl |
MMAF |
Renal cell carcinoma |
ENPP3 |
|
SGN-CD33A |
Hz |
PDB dimer |
AML |
CD33 |
|
SGN-CD19A |
Hz IgG1/maleimidocaproyl |
MMAF |
B cell lymphoma |
CD19 |
|
SGN-LIV1A |
Hz IgG1/V.C |
MMAE |
Metastatic breast cancer |
LIV-1 |
|
RG7596 |
Hz IgG1/V.C |
MMAE |
NHL |
CD79b |
|
ASG-5ME |
Hu IgG2/V.C |
MMAE |
Pancreatic, gastric, an prostate cancers |
SLC44A4 |
|
BAY 79-4620 |
Hu IgG1/V.C |
MMAE |
Advanced solid tumors |
CA-IX |
|
AGS-67E |
Hu IgG2/V.C |
MMAE |
Lymphoid malignancies, leukemia |
CD37 |
|
AMG-172 |
Hu IgG1/MCC |
Maytansine (DM1) |
Clear cell renal cell carcinoma, renal cell adenocarcinoma and carcinoma |
CD27L |
|
AGS15E |
Hu IgG2/[cleavable] |
MMAE |
Metastatic urothelial cancer |
SLITRK6 |
|
GSK2857916 |
Hz IgG1/maleimidocaproyl |
MMAF |
Multiple myeloma |
BCMA |
|
IMGN289 |
Humanized Anti-EGFR Antibody, J2898A/SMCC |
Maytansine (DM1) |
EGFR-positive solid tumors |
EGFR |
|
AMG 595 |
Hu anti-EGFRvIII specific IgG1 antibody/SMCC |
Maytansine DM1 |
Advanced malignant glioma, anaplastic astrocytomas, glioblastoma multiforme |
EGFRvIII |
|
IMGN242 (huC242-DM4) |
Humanized IgG1/huC242 disulfide |
Maytansinoid |
Solid tumors |
CanAg |
|
Phase I/II |
Immunomedics (IMMU)-110 (hLL1-DOX) |
Milatuzumab hydrazone |
Doxorubicin |
Multiple myeloma |
CD74 |
Lorvotuzumab mertansine (IMGN901) |
Humanized IgG1/huC242 disulfide |
Maytansinoid |
Multiple myeloma, solid tumors |
CD56 |
|
IMMU-132 |
Hz IgG1/CL2A |
CPT-11 SN38 |
Colorectal cancer, gastric adenocarcinoma, esophageal cancer, hepatocellular carcinoma |
TROP-2 |
|
Milatuzumab doxorubicin |
Hz IgG1/hydrazone |
Doxorubicin |
Multiple myeloma |
CD74 |
|
HuMax® -TF |
Hu IgG1/V.C |
MMAE |
Solid tumors |
Tissue factor |
|
Phase II |
SAR3419 (huB4-DM4) |
huB4/humanized IgG1 disulfide, Hz IgG1/SPDB |
DM4 |
B cell NHL |
CD19 |
BT062 |
ChIgG4/SPDB, anti-CD138 chimeric IgG4 disulfide |
DM4 |
Multiple myeloma |
CD138, Syndecan1 |
|
Glembatumumab vedotin (CDX-011) |
Hu IgG2/valine-citrullin, anti-CR011 dipeptide |
MMAE |
Breast cancer melanoma, squamous cell carcinoma of lung |
gpNMB |
|
Anti-PSMA ADC |
Hu IgG1/V.C |
MMAE |
Prostate cancer |
PSMA |
|
MLN0264 |
Hu IgG1/V.C |
MMAE |
Gastrointestinal malignancies |
Guanylyl cyclase C |
|
Lorvotuzumab mertansine |
Hz IgG1/SPP |
DM1 |
Solid tumors |
CD56 |
|
PSMA ADC |
Anti-PSMA fully human IgG1/dipeptide |
Auristatin |
Metastatic, hormone-refractory prostate cancer |
PSMA |
|
Phase III |
Inotuzumab ozogamicin (CMC 544) |
Humanized IgG4/G5/44 hydrazone |
Calicheamicin |
B- cell lymphomas, NHL |
CD22 |
FDA Approved |
Gemtuzumab ozogamicin (mylotarg®), Now terminated |
Hu IgG4/hydrazone |
Calicheamicin |
AML |
CD33 |
Trastuzumab-emtansine (Kadcyla®) |
HzIgG1 trastuzumab/thioether |
DM1 |
Metastatic breast cancer |
HER2 |
|
Brentuximab vedotin (Adcetris®) |
Ch IgG1/V.C |
MMAE |
Hodgkin’s lymphoma |
CD30 |
|
Terminated |
LOP628 |
HzIgG1/(noncleavable) |
Maytansine |
AML/C-Kit-positive solid tumors |
cKit |
Extensive research is ongoing to improve all the components of ADCs that can enhance their selectivity and therapeutic efficacy against tumors. Immunohistology, circulating tumor cells and imaging techniques have been used to determine the patient population likely to respond to ADC therapy. Protein scaffolds, which have high binding affinity to antigen, have been utilized as an approach to increase the binding affinity of ADCs, With advances in the development of ADCs , we believe that more and more ADCs will be used as safe and efficacious cancer medicine.
References
1. Sau S, Alsaab HO, Kashaw SK, Tatiparti K, Iyer AK.Advances in antibody-drug conjugates: A new era of targeted cancer therapy.Drug Discov Today. 2017 Jun 13. pii: S1359-6446(17)30078-8.