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

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

–

–

–

–

–