Selinexor doses and dosing schedules
| Schedule . | Dosing interval/week . | Selinexor dose, mg/m2 . | Total patients . | Patients with NHL . | Patients with CLL . | Patients evaluable for response . | No. of DLTs . | DLT . |
|---|---|---|---|---|---|---|---|---|
| A | M/W/F weeks 1 and 3; M/W weeks 2 and 4 | 3 | 1 | 1 | — | 1 | — | — |
| 6 | 1 | 1 | — | 1 | — | — | ||
| 12 | 3 | 3 | — | 3 | — | — | ||
| B | Lead-in week 12 mg/m2 M/W/F; M/W/F weeks 1 and 3; M/W weeks 2 and 4 | 16.8 | 2 | 1 | 1 | 2 | — | — |
| 23 | 3 | 3 | — | 3 | 1 | Grade 4 thrombocytopenia | ||
| 30 | 5 | 3 | 2 | 5 | — | — | ||
| C | M/W | 30 | 4 | 4 | — | 3 | — | — |
| 35 | 20 | 19 | 1 | 20 | — | — | ||
| 40 | 1 | 1 | — | 1 | — | — | ||
| 45 | 3 | 3 | — | 1 | — | — | ||
| 60 | 19 | 19 | — | 14 | — | — | ||
| 70 | 2 | 2 | — | 2 | — | — | ||
| D | M/T | 23 | 4 | 3 | 1 | 4 | — | — |
| E | M/Th | 35 | 2 | 2 | — | 2 | — | — |
| 49 | 3 | 3 | — | 3 | — | — | ||
| F | Once weekly | 80 | 3 | 1 | 2 | 2 | — | — |
| G | M/W weeks 1 and 2 of 3-week cycle | 60 | 2 | 2 | — | 2 | — | — |
| 80 | 1 | 1 | — | 1 | — | — | ||
| Total | — | — | 79 | 72 | 7 | 70 | — | — |
| Schedule . | Dosing interval/week . | Selinexor dose, mg/m2 . | Total patients . | Patients with NHL . | Patients with CLL . | Patients evaluable for response . | No. of DLTs . | DLT . |
|---|---|---|---|---|---|---|---|---|
| A | M/W/F weeks 1 and 3; M/W weeks 2 and 4 | 3 | 1 | 1 | — | 1 | — | — |
| 6 | 1 | 1 | — | 1 | — | — | ||
| 12 | 3 | 3 | — | 3 | — | — | ||
| B | Lead-in week 12 mg/m2 M/W/F; M/W/F weeks 1 and 3; M/W weeks 2 and 4 | 16.8 | 2 | 1 | 1 | 2 | — | — |
| 23 | 3 | 3 | — | 3 | 1 | Grade 4 thrombocytopenia | ||
| 30 | 5 | 3 | 2 | 5 | — | — | ||
| C | M/W | 30 | 4 | 4 | — | 3 | — | — |
| 35 | 20 | 19 | 1 | 20 | — | — | ||
| 40 | 1 | 1 | — | 1 | — | — | ||
| 45 | 3 | 3 | — | 1 | — | — | ||
| 60 | 19 | 19 | — | 14 | — | — | ||
| 70 | 2 | 2 | — | 2 | — | — | ||
| D | M/T | 23 | 4 | 3 | 1 | 4 | — | — |
| E | M/Th | 35 | 2 | 2 | — | 2 | — | — |
| 49 | 3 | 3 | — | 3 | — | — | ||
| F | Once weekly | 80 | 3 | 1 | 2 | 2 | — | — |
| G | M/W weeks 1 and 2 of 3-week cycle | 60 | 2 | 2 | — | 2 | — | — |
| 80 | 1 | 1 | — | 1 | — | — | ||
| Total | — | — | 79 | 72 | 7 | 70 | — | — |
Number of patients per dose and dose schedule. Different dose schedules were tested as the toxicity profile of selinexor emerged through clinical experience. A lead-in week of 12 mg/m2 (schedule B) was tested in an attempt to acclimate patients to treatment before receiving the target dose. The lead-in week proved ineffective and was subsequently abandoned in favor of twice-weekly dosing (schedules C, D, and E). High doses of selinexor administered once weekly in a 4-week cycle or twice weekly in a 2-weeks-on, 1-week-off cycle were also tested (schedules F and G). Monday (M), day 1; Tuesday (T), day 2; Wednesday (W), day 3; Thursday (Th), day 4; Friday (F), day 5.