Table 5.
Characteristics of ADCs and ARCs directed to LSAs.
| Target | mAb (commercial name/originator) | IgG class | Conjugate | Active indications in HMs (highest phase) | Reference |
|---|---|---|---|---|---|
| CD33 | Gemtuzumab ozogamicin (Mylotarg1/UCB) | Hz IgG4 | Calicheamicin | Approved (AML, W) | (120, 121) |
| IV (AML/NCT00161668 aC) | |||||
| III (AML/NCT00136084 bC, NCT00049517 bANR, NCT00372593 bC) | |||||
| II (CML/NCT01019317 bC) | |||||
| II (APL/NCT00413166 bC) | |||||
| I–II (CLL/NCT00038831 bC) | |||||
| Vadastuximab talirine, SGN-CD33A (Seattle Genetics) | Hz IgG1 | PBD | III (AML/NCT02785900 bT) | (122) | |
| I–II (MDS/NCT02706899 bS) | |||||
| I (APL/NCT01902329 bANR) | |||||
| IMGN-779 (ImmunoGen) | N/A | DGN462 | I (AML/NCT02674763 aR) | (123) | |
| AVE9633 (ImmunoGen) | Hz IgG1 | DM4 | I (AML/NCT00543972 aT) disc. | (124) | |
| 225Ac-HuM195, Lintuzumab-Ac225 (PDL BioPharma) | Hz IgG1 | Actinium-225 | III (AML/NCT00006045 bU) | (125) | |
| II (CML/NCT00002800 bC) | |||||
| II (APL/NCT00002609 bC) | |||||
| II (MDS/NCT00997243 bT) | |||||
| I (MM/NCT02998047 aR) | |||||
| CD19 | Coltuximab ravtansine, SAR3419 (Sanofi, ImmunoGen) | Hz IgG1 | DM4 | II (DLBCL/NCT01470456 bC, NCT01472887 aC) | (126) |
| II (B-ALL/NCT01440179 aT) disc. | |||||
| I (B-NHL/NCT00796731 aC) | |||||
| Denintuzumab mafodotin, SGN-CD19A (Seattle Genetics) | Hz IgG1 | MMAF | II (DLBCL/FL/NCT02855359 bR) | (127) | |
| I (B-ALL/NCT01786096 bC) | |||||
| CD20 | 131-I-tositumomab (Bexxar/Corixa Corp.) | m IgG1 | Iodine 131 | Approved (B-NHL, W) | (128) |
| II (MCL/NCT00022945b C) disc. | |||||
| III (FL/NCT00268983b C) | |||||
| II (CLL/NCT00476047b C) | |||||
| Y90-Ibritumomab tiuxetan (Zevalin/Biogen Idec) | m IgG1 | Yttrium 90 | Approved/B-NHL | (129) | |
| III (FL/NCT02063685b R) | |||||
| III (MCL/NCT01510184a T) disc. | |||||
| III (DLBCL/NCT02366663b T) disc. | |||||
| II (CLL/NCT00119392a ANR) | |||||
| II (MM/NCT01207765a T) disc. | |||||
| CD22 | Inotuzumab ozogamicin, CMC-544 (Besponsa/Celltech Group) | Hz IgG4 | Calicheamicin | Approved/ALL | (130) |
| III (AML/NCT03150693b R) | |||||
| III (DLBCL/NCT01232556b T) disc. | |||||
| III (FL/NCT00562965b T) | |||||
| Pinatuzumab vedotin, RG7593 (Genentech) | Hz IgG1 | MMAE | I–II (B-NHL/NCT01691898b ANR) disc. | (131) | |
| Epratuzumab-SN38 (Immunomedics) | Hz IgG1 | SN-38 | Preclinical (B-NHL, B-ALL) | (132) | |
| Epratuzumab I-131 (Immunomedics) | Hz IgG1 | Iodine 131 | Preclinical (B-NHL) disc. | (133) | |
| Moxetumomab pasudotox, CAT-3888 (NCI) | Fv | PE-38 | III (HCL/NCT01829711a ANR) | (134) | |
| II (B-ALL/NCT02338050a T) | |||||
| I/II (CLL/B-NHL/NCT01030536a C) disc. | |||||
| CD79b | Polatuzumab vedotin, RG-759 (Genentech) | Hz IgG1 | MMAE | II (DLBCL/NCT01992653b ANR) | (135) |
| I/II (FL/NCT01691898b ANR) | |||||
| I (CLL/NCT01290549b C) | |||||
| CD138 | Indatuximab ravtansine, BT-062 (BioTest AG) | Ch IgG4 | DM4 | II (MM/NCT01638936a ANR NCT01001442a C) | (136) |
Antibodies that reached clinical studies.
aMonotherapy.
bCombined therapy.
ADCs, antibody-drug conjugates; ARC, antibody-radionuclide conjugates; mAb, monoclonal antibody; HMs, hematological malignancies; Ch, human–mouse chimeric; Fh, fully human; Hz, humanized; m, mouse; Glyco-Fc, glycoengineered Fc fragment; N/A, not available; Fv, fragment variable; AML, acute myeloid leukemia; APL, acute prolymphocytic leukemia; CML, chronic myeloid leukemia; CLL, chronic lymphocytic leukemia; MDS, myelodysplastic syndrome; MM, multiple myeloma; DLBCL, diffuse large B-cell lymphoma; B-ALL, B-cell acute lymphoblastic leukemia; B-NHL, B-cell non-Hodgkin’s lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; HCL, hairy cell leukemia; disc., discontinued in hematological malignancies; NCT, number of clinical trial (clinicaltrials.gov); C, completed; R, recruiting; T, terminated; ANR, active non-recruiting; NYR, not yet recruiting; T, terminated; S, suspended; W, withdrawn; U, unknown; PBD, pyrrolobenzodiazepine dimmers; MMA, monomethyl auristatin; PE-38 Pseudomonas aeruginosa exotoxin A; DGN462, a DNA-alkylating payload; DM4, a cytotoxic maytansinoid; SN-38, an active metabolite of irinotecan.