Table 2.
Antibody-drug conjugates in clinical trials for lymphoid malignancies
| ADC names | Target | Linker | Payload | Indications | Major responses | Status [reference] |
|---|---|---|---|---|---|---|
| Brentuximab vedotin (Adcetrix®) | CD30 | Protease-cleavable (Val-Cit) | MMAE | R/R HL | ORR 75%, CR 34%; OS 40.5 months, PFS 9.3 months; 5-year OS 41%, PFS 22%; | Approved [54] |
| Frontline stage III & IV HL (+ AVD) | ORR 86%, CR 73%, 2-year PFS 81% | Approved [51] | ||||
| Post-ASCT consolidation for HL | PFS 42.9 months, 5-year PFS 59% | Approved [60, 61] | ||||
| R/R systemic ALCL | ORR 86%, CR 57%, 5-year OS 79%, PFS 57%, DOR 25.6 months | Approved [65, 66] | ||||
| R/R PTCL (+ CHP) | ORR 83%, CR 68%, PFS 48.2 months | Approved [67] | ||||
| R/R CTCL | ORR 56.3%, CR 16%, PFS 17.2 months | Approved [68] | ||||
| Inotuzumab ozogamicin (Besponsa®) | CD22 | Acid-labile (hydrazone) | Calicheamicin | R/R B-cell ALL, | CR/CRi 73.8%, OS 7.7 mo, PFS 5 months | Approved [74, 75] |
| Frontline Ph- B-cell ALL (+ miniHCVD) | ORR 98%, CR 85%, 3-year OS 56%, PFS 49% | Phase II [82] | ||||
| R/R B-cell NHL | ORR 67%, CR 31%, PFS 12.7 months | Phase II [89] | ||||
| Moxetumomab pasudotox (Lumoxiti®) | CD22 | Disulfide bond | PE38 | R/R HCL | ORR 75%, CR 41%, PFS not reached at 16.7-month follow up | Approved [97, 98] |
| Polatuzumab vedotin (DCDTS4501A) | CD79b | Protease-cleavable (Val-Cit) | MMAE | R/R DLBCL (+ BR) | ORR 63%, PFS 7.6 months, OS 12.4 months | Approved [103] |
| Newly diagnosed DLBCL (+ G-CHP or + R-CHP) |
G-CHP: ORR 91%, CR 81%; R-CHP: ORR 91%, CR 78%; |
Phase III [105, 106] | ||||
| Coltuximab ravtansine (SAR3419) | CD19 | Disulfide bond (SPDB) | DM4 | R/R DLBCL | ORR 43.9%, CR 14.6%, OS 9.2 months, PFS 4.4 months | Phase II [109] |
| Denintuzumab mafodotin (SGN-CD19A) | CD19 | Non-cleavable (MC) | MMAF | R/R B-cell ALL | ORR 35%, CR 19%, DOR 27 weeks | Phase I [110] |
| R/R DLBCL | ORR 33%, CR 22%, DOR 40 weeks | Phase I [111] | ||||
| Loncastuximab Tesirine (ADCT-402) | CD19 | Protease-cleavable (Val-Ala) | PBD dimer | R/R B-cell ALL | CR 8.7% | Phase I [112] |
| R/R NHL |
DLBCL: ORR 40.2%, CR 22% MCL: ORR 46.7%, CR 26.7%; FL: ORR 80%, CR 53.3% |
Phase I [113, 114] | ||||
| Pinatuzumb vedotin (DCDT2980S) | CD22 | Protease-cleavable (Val-Cit) | MMAE | R/R B-cell NHL (+ Rituximab) | DLBCL: ORR 60%, CR 26%, PFS 5.4 months; FL: ORR 62%, CR 5%, PFS 12.7 months | Phase II [103] |
| Camidanlumab tesirine (ADCT-301) | CD25 | Protease-cleavable (Val-Ala) | PBD dimer | R/R HL | ORR 80.8%, CR 50%, DOR 7.7 months, PFS 6.7 months | Phase I [115] |
| R/R B and T cell NHL |
B: ORR 31.3%, CR 18.8%; T: ORR 50%, CR 0 |
Phase I [116] | ||||
| Naratuximab emtansine (IMGN529) | CD37 | Non-cleavable (SMCC) | DM1 | R/R B-cell NHL | ORR 13%, CR 2.6% | Phase I [117] |
| AGS67E | CD37 | Protease-cleavable (Val-Cit) | MMAE | R/R B and T cell NHL | ORR 22%, CR 14% | Phase I [118] |
ADC antibody-drug conjugate, ALCL anaplastic large cell lymphoma, ALL acute lymphoblastic leukemia, CTCL cutaneous T cell lymphoma, HL Hodgkin lymphoma, NHL non-Hodgkin lymphoma, R/R relapsed/refractory, MM multiple myeloma, CR complete remission, DLBCL diffuse large cell lymphoma, DOR duration of response, FL follicular lymphoma, MCL mantle cell lymphoma, ORR overall response rate, OS overall survival, PFS progression-free survival, PTCL peripheral T cell lymphoma