Treatment schedule and dose
| Dose-escalation phase . | Dose level . | Patients (n) . | Selinexor, mg PO . | Dexamethasone, mg PO . | Bortezomib, mg/m2 SC . |
|---|---|---|---|---|---|
| Days 1, 8, 15, 22, 29 . | Days 1, 8, 15, 22, 29 . | Days 1, 8, 15, 22 . | |||
| Cohort 1. Once-weekly selinexor in a 35-d cycle | 1 2 | 4 6 | 80 100 | 40 40 | 1.3 1.3 |
| Dose-escalation phase . | Dose level . | Patients (n) . | Selinexor, mg PO . | Dexamethasone, mg PO . | Bortezomib, mg/m2 SC . |
|---|---|---|---|---|---|
| Days 1, 8, 15, 22, 29 . | Days 1, 8, 15, 22, 29 . | Days 1, 8, 15, 22 . | |||
| Cohort 1. Once-weekly selinexor in a 35-d cycle | 1 2 | 4 6 | 80 100 | 40 40 | 1.3 1.3 |
| . | . | . | Days 1, 8, 15 . | Days 1, 8, 15 . | Days 1, 4, 8, 11 . |
|---|---|---|---|---|---|
| Cohort 1. Once-weekly selinexor in a 21-d cycle | 3 | 3 | 80 | 40 | 1.3 |
| . | . | . | Days 1, 8, 15 . | Days 1, 8, 15 . | Days 1, 4, 8, 11 . |
|---|---|---|---|---|---|
| Cohort 1. Once-weekly selinexor in a 21-d cycle | 3 | 3 | 80 | 40 | 1.3 |
| . | . | . | Days 1, 3, 8, 10, 15, 17, 22, 24 . | Days 1, 3, 8, 10, 15, 17, 22, 24, 29, 31 . | Days 1, 8, 15, 22 . |
|---|---|---|---|---|---|
| Cohort 2. Twice-weekly selinexor in a 35-d cycle | 1 2 | 3 6 | 60 80 | 20 20 | 1.3 1.3 |
| . | . | . | Days 1, 3, 8, 10, 15, 17, 22, 24 . | Days 1, 3, 8, 10, 15, 17, 22, 24, 29, 31 . | Days 1, 8, 15, 22 . |
|---|---|---|---|---|---|
| Cohort 2. Twice-weekly selinexor in a 35-d cycle | 1 2 | 3 6 | 60 80 | 20 20 | 1.3 1.3 |
| . | . | . | Days 1, 8, 15, 22, 29 . | Days 1, 8, 15, 22, 29 . | Days 1, 8, 15, 22 . |
|---|---|---|---|---|---|
| RP2D | 20 | 100 | 40 | 1.3 |
| . | . | . | Days 1, 8, 15, 22, 29 . | Days 1, 8, 15, 22, 29 . | Days 1, 8, 15, 22 . |
|---|---|---|---|---|---|
| RP2D | 20 | 100 | 40 | 1.3 |
Treatment schedule and starting dose for patients treated with SVd. During the dose-escalation phase, patients were randomized to receive selinexor once weekly or twice weekly in 21- or 35-d cycles, depending on the bortezomib dosing schedule (cohort 1 or 2). Dose escalation proceeded after DLTs were cleared at dose level 1. Based on the opinions of the investigators, the side effects of SVd, when bortezomib was given twice weekly in 21-d cycles (cohort 1, dose level 3), were not sustainable for long-term treatment, and therefore, this dosing schedule was abandoned. The dose-expansion phase enrolled an additional 20 patients at the RP2D to better understand the safety and efficacy of SVd in a once-weekly schedule.
PO, orally; SC, subcutaneously.