Key studies of marizomib and MLN9708 in relapsed/refractory and frontline MM
| Study . | Regimen . | N . | Response rates, % . | Outcomes, % . | Toxicities, % . |
|---|---|---|---|---|---|
| Marizomib | |||||
| Combined phase 1 analysis93 | Marizomib* ± dex | 34 | Dose 0.4-0.6 mg/m2; ORR: 20 | NR | Most common: fatigue, nausea, vomiting, dizziness, headache, diarrhea, constipation, insomnia, anorexia, dyspnea |
| MLN9708 | |||||
| Phase 1, rel/ref MM97 | Oral MLN9708 BIW† | 56 | ≥ MR: 15; ORR: 13; CR: 2 | DOR: up to 16 mo | Grade 3/4 AEs: thrombocytopenia 34; neutropenia 14; fatigue 9; rash 9 |
| Phase 1, rel/ref MM96 | Oral MLN9708 QW‡ | 28 | 1 PR in 16 evaluable patients | DOR: 3.7+ mo | Common drug-related AEs: fatigue 39; thrombocytopenia 36; nausea 32; diarrhea 29 |
| Phase 1, frontline MM95 | MLN9708-len-dex | 10 | ORR: 100; ≥ VGPR: 44 | NR | Grade 3 AEs include: fainting; DVT; gastrointestinal hemorrhage; hypotension |
| Study . | Regimen . | N . | Response rates, % . | Outcomes, % . | Toxicities, % . |
|---|---|---|---|---|---|
| Marizomib | |||||
| Combined phase 1 analysis93 | Marizomib* ± dex | 34 | Dose 0.4-0.6 mg/m2; ORR: 20 | NR | Most common: fatigue, nausea, vomiting, dizziness, headache, diarrhea, constipation, insomnia, anorexia, dyspnea |
| MLN9708 | |||||
| Phase 1, rel/ref MM97 | Oral MLN9708 BIW† | 56 | ≥ MR: 15; ORR: 13; CR: 2 | DOR: up to 16 mo | Grade 3/4 AEs: thrombocytopenia 34; neutropenia 14; fatigue 9; rash 9 |
| Phase 1, rel/ref MM96 | Oral MLN9708 QW‡ | 28 | 1 PR in 16 evaluable patients | DOR: 3.7+ mo | Common drug-related AEs: fatigue 39; thrombocytopenia 36; nausea 32; diarrhea 29 |
| Phase 1, frontline MM95 | MLN9708-len-dex | 10 | ORR: 100; ≥ VGPR: 44 | NR | Grade 3 AEs include: fainting; DVT; gastrointestinal hemorrhage; hypotension |
dex indicates dexamethasone; rel/ref, relapsed/refractory; BIW, twice weekly; MR, minimal response; DOR, duration of response; QW, once-weekly; and len, lenalidomide.
Marizomib dosed at 0.075 to 0.6 mg/m2 IV on days 1, 4, 8, and 11 of 21-day cycles.
MLN9708 dosed at 0.24 to 2.33 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles.
MLN9708 dosed at 0.24 to 3.95 mg/m2 on days 1, 8, and 15 of 28-day cycles.