Table 1.
Summary of the most relevant clinical trials with novel proteasome inhibitors in monotherapy in relapsed/refractory MM
| Drug | Trial | Phase | n | prior lines | Dose | Schedule | ORR (≥ PR) | BR (≥ MR) | PFS (month) | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| Carfilzomib (PR-171) | PX-171-001 | 1 | 10 MM | - | MTD: 15 mg/m2 | 1–5/14d | 10% | 20% | - | O’Connor. CCR 2009175 |
| PX-171-002 | 1 | 28 | - | Recommended dose: 20 mg/m2 initially 27 mg/m2 from C1D8 |
1–2, 8–9, 15–16/28d | 19% | 27% | - | Alsina. CCR 2012176 |
|
| PX-171- 003A0 | 2 | 46 | 5 (2–16) | 20 mg/m2 | 1–2, 8–9, 15–16/28d | 17% | 24% | 3.5 | Jagannath. Clin Lymph Myeloma 2012177 |
|
| PX-171- 003A1 | 2 | 266 | 5 (1–20) | 20 mg/m2 in C1 27 mg/m2 from C2 |
1–2, 8–9, 15–16/28d | 24% | 37% | 3.7 | Siegel. Blood 2012178 |
|
| PX-171-004 | 2 | 129 Btz naïve patients | 2 (1–4) | C-1: 20 mg/m2 C-2: 20 mg/m2 in C1 27 mg/m2 from C2 |
1–2, 8–9, 15–16/28d | C-1: 42% C-2: 52% |
C-1: 59% C-2: 64% |
C-1: 8.2 C-2: NR |
Vij Blood 201221 | |
| 35 Btz treated patients | 3 (1–13) | 20 mg/m2 | 1–2, 8–9, 15–16/28d | 17% | 31% | 4.6 | Vij BJH 201223 | |||
| PX-171-005 | 2 | 50 (Renal impairment) | 5 (1–15) | 15 mg/m2 in C1 20 mg/m2 in C2 27 mg/m2 from C3 |
1–2, 8–9, 15–16/28d | 26% | 32% | - | Badros. Leukemia 201325 |
|
| Ixazomib (MLN-9708) | C16004 | 1 | 60 | 6 (2–18) | MTD: 2.97 mg/m2 | 1, 8, 15/28d | 15% | 17% | - | Kumar. ASCO 201343 |
| C16003 | 1 | 57 | 4 (1–28) | MTD: 2 mg/m2 | 1, 4, 8, 11/21d | 13% | 15% | - | Lonial. ASCO 201244 |
|
| Marizomib (NPI-0052) | NPI-0052-101 NPI-0052-102 |
1 | 34 | 6 | MTD: 0.4 mg/m2 in 1 h inf. & 0.5 mg/m2 in 2 h inf. | 1, 4, 8, 11/21d | 14% | 14% | - | Richardson. ASH 201147 |
MED: Minimum effective dose
MTD: Maximum tolerated dose
NR: Not reached