Table 1.
Trials of daratumumab performed to date.
| Trial | Population | Response | PFS/OS | ||
|---|---|---|---|---|---|
| GEN501 Lokhorst et al. [2015] | Phase I/II daratumumab monotherapy; | RRMM; median 4 prior lines; 64% refractory to both PI/IMiD | Part 1: dose escalation (n = 32); Part 2: (n = 72) expansion cohort, 16 mg/kg | Part 1: 4PR, 3MR in 12 patients who received daratumumab 4–24 mg/kg; Part 2: ORR: 36% | OS: NR at median follow up 10.2 months PFS: 5.6 months |
| SIRIUS Lonial et al. [2016b]
|
Phase II daratumumab monotherapy; | RRMM; 95% double-refractory; median 5 prior lines |
N = 106 Part 1: 8 mg/kg (n = 18); 16 mg/kg (n = 16); Part 2: n = 106 16 mg/kg |
ORR: 29%, DOR 7.4 months, PFS 3.7 months | OS: 1-year survival rate 64.8%; subsequent cut-off: OS 17.5 months |
| GEN501/SIRIUS Usmani et al. [2016] |
Combined analysis | RRMM; median 5 prior lines | N = 148; 16 mg/kg | ORR: 31% DOR: 7.6 months | 1 year PFS: 46% median follow up 9.3 months; 1 year estimated OS: 69% |
| GEN503 Plesner et al. [2014, 2015] |
Phase I/II DARA + LEN/DEX LEN 25 mg d1-21/28 DEX 40 mg weekly | RRMM; Part 2 excluded LEN-refractory patients; ⩾1 prior line | Part 1 (n = 13): dose-escalation 2–16 mg/kg; Part 2 (n = 32): expansion cohort 16 mg/kg | Part 1: ORR 100% Part 2: ORR 81%: 63% ⩾VGPR; 9% CR; 25% sCR | 18-month PFS: 72% 18-month OS: 90% |
| Mateos et al. [2016]; Chari et al. [2015] | Phase Ib: daratumumab + backbone agents in NDMM & RRMM | NDMM: DARA + VD or VMP or VTD; RRMM: DARA + POM + DEX; median 4 prior lines 66% double-refractory | NDMM: n = 25 RRMM: n = 24 RRMM: n = 98 | NDMM: ORR 100% RRMM ORR: 54.5% RRMM: ORR 71%; 33% VGPR; 94% CR, 5% sCR Double-refractory disease: ORR 67% | 6-month PFS 66% |
| CASTOR Palumbo et al. [2016] | Phase III: DARA + bortezomib/DEX versus bortezomib/DEX | RRMM; median 2 prior lines; 66% prior PI | N = 498 | ORR: DVD: 83% VD: 63% | PFS: DVD, NR. VD, 7.1 months; 61% reduction in risk of progression |
| POLLUX [Dimopoulos et al. 2016] | Phase III: DARA + LEN/DEX versus LEN/DEX | RRMM; Median 1 prior line; 18% prior LEN, none refractory | N = 569 | ORR: DRd: 93% Rd: 76% | PFS: DRd: NR Rd: 18.4 63% reduction in risk of progression |
ASCT, autologous stem cell transplantation; CR, complete remission; DARA, daratumumab; DEX, dexamethasone; DOR, duration of response; DVD, DARA, bortezomib, and DEX; IMiD, immunomodulatory drugs; LEN, lenalidomide; MM, multiple myeloma; MR, NDMM, newly diagnosed multiple myeloma; NR, not reached; ORR, overall response rate; OS, overall survival; PI, proteasome inhibitors; PFS, progression-free survival; POM, pomalidomide; PR, partial response; RRMM, relapsed/refractory multiple myeloma; VGPR, very good partial response; sCR, stringent complete remission; VD, bortezomib and DEX; VMP, bortezomib, melphalan, prednisone; VTD, bortezomib, thalidomide, dexamethasone.