Table 1.
Clinical efficacy of ixazomib in patients with MM
| Study | Phase | Na | Regimen | Ixazomib dose schedule | Prior therapy | ORR | Outcomes |
|---|---|---|---|---|---|---|---|
| Single-agent ixazomib | |||||||
| C1600349 | 1 | 55/60 | Ixazomib twice-weekly (days 1, 4, 8, and 11 of 21-d cycles) | MTD 2.0 mg/m2 twice-weekly | Median 4 lines | 1 CR, 1 VGPR, 6 PR, 1 MR | NR |
| C1600448 | 2 | 50/60 | Ixazomib weekly (days 1, 8, and 15 of 28-d cycles) | MTD 2.97 mg/m2 weekly | Median 4 lines | 1 VGPR, 8 PR, 1 MR | NR |
| Mayo Clinic phase 264 | 2 | 32/33 | Ixazomib ± dex | 5.5 mg weekly | Median 2 therapies | ORR 34%; 2 sCR, 3 PR with ixazomib alone, + 6 PR with added Dex | EFS 12.4 mos 6-mo OS 96% |
| Mayo Clinic phase 265 | 2 | 71 | Ixazomib | 4 mg vs 5.5 mg weekly | Median 4 therapies | ORR 31% ORR 51% |
NR |
| Ixazomib–Rd | |||||||
| TOURMALINE-MM1 (C16010)6 | 3 | 360 | Ixazomib–Rd vs | 4 mg weekly | 62%/27%/11% | ORR 78%, ≥VGPR 48%, CR 12% | HR 0.74, p=0.01 |
| 362 | Placebo–Rd | 60%/31%/9% (1/2/3 prior therapies) | ORR 72%, ≥VGPR 39%, CR 7% | Median PFS 20.6 mos vs 14.7 mos | |||
| C1600547 | 1/2 | 65 | Ixazomib–Rd | 4 mg weekly | None | ORR 92%; ≥VGPR 58%; CR + nCR 34%; CR 27% | 1-year PFS: 88% |
| C1600860 | 1/2 | 65 | Ixazomib–Rd | 3 mg twice-weekly | None | ORR 94%; ≥VGPR 76%; CR + nCR 36%; CR/sCR 26% | NR |
| C1601357 | 1 | 43 | Ixazomib–Rd, Asian pts | 4 mg weekly | 47/23/29 (1/2/3 prior therapies) | ORR 65%; ≥VGPR 23%; CR 9% | NR |
| Other combinations | |||||||
| C16006 | 2 | 16 | Ixazomib twice-weekly + MP | 6/9 | None | 1 sCR, 4 PR | NR |
| 6/9 | Ixazomib weekly + MP | 7/7 | None | 4 PR | NR | ||
| C1602061 | 2 | 36 34 |
Ixazomib–Cd (C 300 mg vs C 400 mg) | 4 mg weekly | None | ORR 78%, ≥VGPR 28% ORR 65%, ≥VGPR 21% |
12-mo PFS 68% vs 91% |
| Case Comprehensive Cancer Center75 | 1 | 11 | Ixazomib + panobinostat + dex | 4 mg weekly | Median 5 therapies | 3 MR | NR |
| Alliance76 | 1 | 17 | Ixazomib + pomalidomide + dex | 3–4 mg weekly | All pts had received prior lenalidomide, bortezomib, and dex | In 13 pts receiving >1 cycle of therapy: ORR 62%, ≥VGPR 8% | NR |
| City of Hope Medical Center74 | 1 | 21 | Ixazomib + pomalidomide + dex | 3–4 mg weekly | Median 3 therapies | In 9 response-evaluable pts, ORR 33% | NR |
Notes:
a
Number of response-evaluable patients/total number of treated patients.
Abbreviations: Cd, cyclophosphamide-dexamethasone; CR, complete response; dex, dexamethasone; EFS, event-free survival; mo(s), month(s); HR, hazard ratio; MM, multiple myeloma; MP, melphalan–prednisone; MR, minimal response; MTD, maximum tolerated dose; nCR, near complete response; NR, not reported; ORR, overall response rate; OS, overall survival; PR, partial response; pts, patients; Rd, lenalidomide-dexamethasone; sCR, stringent CR; VGPR, very good partial response