Table 1.
BCMA-targeted antibody-drug conjugates in clinical trials
| Name | Structure | Clinical trial information | Inclusion/exclusion criteria | Pt characteristics | Dosage | Major response | Most common AE |
|---|---|---|---|---|---|---|---|
| Belantamab mafodotin (GSK2857916) |
Linker: non-cleavable MC Payload: MMAF |
Phase 1 NCT02064387, DREAMM-1 |
R/R MM received or were refractory to ASCT, alkylators, PI, and IMiD |
35 pts in dose expansion phase; median age 60; high-risk cytogenetics 13 (37%); 14 (40%) pts received > 5 prior lines; mDOF: 12.5 mo |
3.4 mg/kg every 3 wks |
ORR 60%; sCR 2 (6%), CR 3 (9%), VGPR 14 (40%); mPFS 12 mo; mDOR 14.3 mo |
G3+ thrombocytopenia (35%) anemia (17%); G1,2 corneal events: blurry vision (52%), dry eyes (37%), |
|
Phase 2 NCT03525678, DREAMM-2 [70] |
R/R MM received or were refractory to ≥ 3 anti-MM therapies, including ASCT, alkylators, PI, IMiD, and CD38 mAb |
196 pts − 2.5 mg/kg cohort 97 pts; median age 65; high-risk cytogenetics 41 (42%); median prior therapies 7; mDOF 6.3 mo − 3.4 mg/kg cohort: 99 pts; median age 67; high-risk cytogenetics 47 (47%); median prior therapies 6; mDOF 6.9 mo |
2.5 or 3.4 mg/kg every 3 wks |
− 2.5 mg/kg cohort: ORR 30 (31%); sCR/CR 3 (3%), VGPR 15 (15%); PD 56 (58%); mPFS 2.9 mo; − 3.4 mg/kg cohort: ORR 34 (34%); sCR/CR 3 (3%), VGPR 17 (17%); PD 55 (56%); mPFS 4.9 mo; |
G3+ keratopathy (27% in the 2.5 mg/kg cohort and 21% in the 3.4 mg/kg cohort), thrombocytopenia (20% and 33%), and anemia (20% and 25%). TRD 2 |
||
| MEDI2228 |
Linker: protease-cleavable Payload: PBD |
Phase 1 |
R/R MM received or were refractory to all standard therapy including PI, IMiD, and ASCT | – | – | – | – |
| HDP-101 |
Linker: non-cleavable MC Payload: Amanitin |
Preclinical | – | – | – | – | – |
AE adverse event, CR complete response, G grade, mDOF median duration of follow-up, MC maleimidocaproyl, MMAF monomethyl auristatin F, mo month, mDOR median duration of response, mPFS median progression-free survival, ORR overall response rate, PBD pyrrolobenzodiazepine, PD progressive disease, pt patient, sCR stringent complete response, VGPR very good partial response, wk week