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Table 1 BCMA-targeted antibody-drug conjugates in clinical trials

From: BCMA-targeted immunotherapy for multiple myeloma

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
[74, 85]
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
NCT03489525,
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
  1. 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