Patient disposition by study phase and treatment in phase 1b and phase 2 stage 1 (full analysis set)
| . | Phase 1b dose-escalation phase, n (%) . | Phase 1b dose expansion phase and phase 2 stage 1, n (%) . | . | ||
|---|---|---|---|---|---|
| Reasons for discontinuation of treatment . | Sonidegib 400 mg + ruxolitinib 10 mg (n = 8) . | Sonidegib 400 mg + ruxolitinib 15 mg (n = 10) . | Sonidegib 400 mg + ruxolitinib 20 mg (n = 5) . | Sonidegib 400 mg + ruxolitinib 20 mg (n = 27) . | All patients (N = 50), n (%) . |
| AEs* | 2 (25.0) | 5 (50.0) | 2 (40.0) | 16 (59.3) | 25 (50.0) |
| Completed | 0 (0.0) | 1 (10.0) | 0 (0.0) | 0 (0.0) | 1 (2.0) |
| Death† | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (3.7) | 1 (2.0) |
| Physician’s decision | 2 (25.0) | 2 (20.0) | 1 (20.0) | 2 (7.4) | 7 (14.0) |
| Progressive disease | 2 (25.0) | 2 (20.0) | 1 (20.0) | 1 (3.7) | 6 (12.0) |
| Study terminated by sponsor | 0 (0.0) | 0 (0.0) | 1 (20.0) | 3 (11.1) | 4 (8.0) |
| Patient/guardian decision | 2 (25.0) | 0 (0.0) | 0 (0.0) | 4 (14.8) | 6 (12.0) |
| . | Phase 1b dose-escalation phase, n (%) . | Phase 1b dose expansion phase and phase 2 stage 1, n (%) . | . | ||
|---|---|---|---|---|---|
| Reasons for discontinuation of treatment . | Sonidegib 400 mg + ruxolitinib 10 mg (n = 8) . | Sonidegib 400 mg + ruxolitinib 15 mg (n = 10) . | Sonidegib 400 mg + ruxolitinib 20 mg (n = 5) . | Sonidegib 400 mg + ruxolitinib 20 mg (n = 27) . | All patients (N = 50), n (%) . |
| AEs* | 2 (25.0) | 5 (50.0) | 2 (40.0) | 16 (59.3) | 25 (50.0) |
| Completed | 0 (0.0) | 1 (10.0) | 0 (0.0) | 0 (0.0) | 1 (2.0) |
| Death† | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (3.7) | 1 (2.0) |
| Physician’s decision | 2 (25.0) | 2 (20.0) | 1 (20.0) | 2 (7.4) | 7 (14.0) |
| Progressive disease | 2 (25.0) | 2 (20.0) | 1 (20.0) | 1 (3.7) | 6 (12.0) |
| Study terminated by sponsor | 0 (0.0) | 0 (0.0) | 1 (20.0) | 3 (11.1) | 4 (8.0) |
| Patient/guardian decision | 2 (25.0) | 0 (0.0) | 0 (0.0) | 4 (14.8) | 6 (12.0) |
The most frequently reported (≥5% of patients) AEs leading to study drug discontinuation were increased blood creatine phosphokinase, thrombocytopenia, muscle spasms, AML, and alopecia.
On-treatment death due to multiple organ dysfunction syndrome: 4 deaths were reported during the study; the remaining 3 patients discontinued their treatment due to “progressive disease” (n = 2) and an AE (n = 1).