Table 6.
Characteristics of ADCs and ARCs directed to NLSAs.
| Target | mAb (commercial name/originator) | IgG class | Conjugate | Active indications in HMs (highest phase) | Reference |
|---|---|---|---|---|---|
| CD25 | ADCT-301, HuMax-TAC-PBD (ADC Therapeutics; Genmab) | Fh IgG1 | PBD | I (AML/B-ALL/NCT02588092 aR) | (137) |
| I (HL, B-NHL, PTCL, CTCL/NCT02432235 aR) | |||||
| IMTOX-25, RFT5-DGA (XOMA) | mIgG1 | DGA | II (ATL/NCT01378871a C) disc. | (138) | |
| II (T-NHL/NCT00667017a C) disc. | |||||
| anti-Tac(Fv)-PE38, LMB-2 (NCI) | Fv | PE-38 | II (HCL/NCT00321555 aANR, NCT00923013 bR) | (139) | |
| II (CTCL/NCT00080535 aC) | |||||
| II (CLL/NCT00077922 aC) disc. | |||||
| I–II (ATLL/NCT00924170 bANR) | |||||
| CD30 | Brentuximab vedotin, SGN-35 (Adcetris/Seattle Genetics) | Ch IgG1 | MMAE | Approved (ALCL, HL) | (140) |
| Preregistration (CTCL) | |||||
| III (CTCL/NCT01578499 aANR) | |||||
| III (SS/NCT01578499 aANR) | |||||
| III (T-cell lymphoma/NCT01777152 aANR) | |||||
| II (DLBCL/NCT02734771 bR, NCT01925612 bT) | |||||
| II (AML/NCT01461538 bC) | |||||
| II (FL, MZL/NCT02623920 bW, NCT02594163 bANR) | |||||
| II (MF/SS/PTCL/NCT01352520 aANR, NCT03113500 bR) | |||||
| I–II (NK-T lymphoma/NCT03246750 bNYR) | |||||
| CD37 | AGS67E (Agensys) | Fh IgG2 | MMAE | I (AML/NCT02610062 aR) | (79) |
| I (B-NHL/NCT02175433 aR) | |||||
| IMGN529, K7153A (ImmunoGen) | Hz IgG1 | DM1 | II (DLBCL/NCT02564744 bR) | (141) | |
| I (CLL, B-NHL/NCT01534715 aC) | |||||
| 177Lu-tetulomab, lilotomab (Betalutin/Nordic Nanovector) | Mouse N/A | Lutetium 177 | I–II (B-NHL/NCT01796171 aR) | (142) | |
| I (DLBCL/NCT02658968 aR) | |||||
| CD56 | Lorvotuzumab mertansine, IMGN-901 (ImmunoGen) | Hz IgG1 | DM1 | II (AML, NK-cell leukemia, B-ALL CML, MF/NCT02420873a C) | (143) |
| I (MM/NCT00991562 bC/NCT00346255 aC) | |||||
| CD70 | Vorsetuzumab mafodotin, SGN-75 (Seattle Genetics) | Hz IgG1 | MMAF | I (B-NHL/NCT01015911a C) disc. | (144) |
| Lack of efficacy; second generation SGN-70A | |||||
| SGN-70A (Seattle Genetics) | Hz IgG1 | PBD | I (DLBCL, MCL, FL/NCT02216890a C) disc. (superseding SGN-75) | (145) | |
| MDX-1203 (Medarex) | Fh IgG1 | MED-2460 | I (B-NHL/NCT00944905a C) | (146) | |
| CD74 | Milatuzumab-doxorubicin, IMMU-110 (Immunomedics) | Hz IgG1 | Doxorubicin | I–II (MM/NCT01101594a C) | (147) |
| CD117 | LOP-628 (Novartis) | Hz IgG1 | Maytansine | I (AML/NCT02221505a T) disc. | |
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; N/A, not available; Fv, fragment variable; AML, acute myeloid leukemia; HL, Hodgkin’s lymphoma; B-ALL, B-cell acute lymphoblastic leukemia; B-NHL, B-cell non-Hodgkin’s lymphoma; PTCL, peripheral T-cell lymphoma; CTCL, cutaneous T-cell lymphoma; ATL, adult T-cell leukemia and lymphoma; HCL, hairy cell leukemia; CLL, chronic lymphocytic leukemia; ALCL, anaplastic large-cell lymphoma; SS, Sézary syndrome; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MZL, marginal zone lymphoma; MF, mycosis fungoides; CML, chronic myeloid leukemia; MM, multiple myeloma; MCL, mantle cell lymphoma; 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; DGA (deglyscosylated ricin A-chain); PE-38 Pseudomonas aeruginosa exotoxin A; MMA, monomethyl auristatin; DM1, a cytotoxic maytansinoid; MED-2460, a DNA-alkylating payload.