Treatment regimens
| Stages and dosing schedule . | Regimen . | Formulation used . | Cohort . | Doses . | Number of patients who received Dex* . | Number of patients who received MRZ† . |
|---|---|---|---|---|---|---|
| Stages 1-3: schedule A, once weekly | Days 1, 8, and 11, 4-wk cycles, 1 or 10 min | IV liquid | −3 | 0.025 mg/m2 | 0 | 3 |
| −2 | 0.05 mg/m2 | 0 | 3 | |||
| −1 | 0.075 mg/m2 | 0 | 7 | |||
| 1 | 0.15 mg/m2 | 0 | 2 | |||
| 2 | 0.3 mg/m2 | 0 | 1 | |||
| 3 | 0.6 mg/m2 | 0 | 3 | |||
| 4/RP2D§ | 0.7 mg/m2 | 0 | 8 | |||
| IV lyophile‡ | Expanded RP2D*,§ | 0.7 mg/m2 | 0 | 5 | ||
| Stages 4 and 5: schedule B, twice weekly | Days 1, 4, 8, and 11, 3-wk cycles, 1 or 2 h | IV lyophile | 1 | 0.15 mg/m2 | 1 | 3 |
| 2 | 0.4 mg/m2 | 3 | 4 | |||
| 3 | 0.5 mg/m2 | 1 | 2 | |||
| 4 | 0.6 mg/m2 | 3 | 3 | |||
| RP2D§ | 0.5 mg/m2 | 15 | 24 |
| Stages and dosing schedule . | Regimen . | Formulation used . | Cohort . | Doses . | Number of patients who received Dex* . | Number of patients who received MRZ† . |
|---|---|---|---|---|---|---|
| Stages 1-3: schedule A, once weekly | Days 1, 8, and 11, 4-wk cycles, 1 or 10 min | IV liquid | −3 | 0.025 mg/m2 | 0 | 3 |
| −2 | 0.05 mg/m2 | 0 | 3 | |||
| −1 | 0.075 mg/m2 | 0 | 7 | |||
| 1 | 0.15 mg/m2 | 0 | 2 | |||
| 2 | 0.3 mg/m2 | 0 | 1 | |||
| 3 | 0.6 mg/m2 | 0 | 3 | |||
| 4/RP2D§ | 0.7 mg/m2 | 0 | 8 | |||
| IV lyophile‡ | Expanded RP2D*,§ | 0.7 mg/m2 | 0 | 5 | ||
| Stages 4 and 5: schedule B, twice weekly | Days 1, 4, 8, and 11, 3-wk cycles, 1 or 2 h | IV lyophile | 1 | 0.15 mg/m2 | 1 | 3 |
| 2 | 0.4 mg/m2 | 3 | 4 | |||
| 3 | 0.5 mg/m2 | 1 | 2 | |||
| 4 | 0.6 mg/m2 | 3 | 3 | |||
| RP2D§ | 0.5 mg/m2 | 15 | 24 |
Dex, if administered, was instructed to be administered on the day of and the day after MRZ dosing.
Data from study NPI-0052-102 provided safety information to allow some dose levels (0.15 mg/m2 and 0.3 mg/m2) to be bypassed with fewer than 3 patients enrolled.
On schedule A, all patients who were dosed prior to the RP2D cohort received the liquid formulation; the 5 schedule A patients in the RP2D cohort received the lyophile formulation by crossover (ie, alternate assignment of patients to receive their first dose using either the lyophile or liquid formulation).
The schedule A RP2D was established as 0.7 mg/m2 infused over 10 minutes, and the schedule B RP2D was 0.5 mg/m2 infused over 2 hours.