AEs (≥20% of patients), regardless of study drug relationship (safety analysis set)
| . | Phase 1b dose-escalation phase, n (%) . | Phase 1b dose expansion phase and phase 2 stage 1. n (%) . | All patients (N = 50), n (%) . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 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 grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . |
| Total | 8 (100) | 8 (100) | 10 (100) | 8 (80) | 5 (100) | 4 (80) | 27 (100) | 19 (70.4) | 50 (100) | 39 (78) |
| Muscle spasms* | 3 (37.5) | 0 (0.0) | 6 (60.0) | 1 (10.0) | 4 (80.0) | 0 (0.0) | 18 (66.7) | 1 (3.7) | 31 (62.0) | 2 (4.0) |
| Myalgia* | 1 (12.5) | 0 (0.0) | 3 (30.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 10 (37.0) | 2 (7.4) | 14 (28.0) | 2 (4.0) |
| Fatigue | 6 (75.0) | 1 (12.5) | 3 (30.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 8 (29.6) | 0 (0.0) | 17 (34.0) | 1 (2.0) |
| Pyrexia | 2 (25.0) | 2 (25.0) | 2 (20.0) | 0 (0.0) | 2 (40.0) | 0 (0.0) | 9 (33.3) | 2 (7.4) | 15 (30.0) | 4 (8.0) |
| Cough | 1 (12.5) | 0 (0.0) | 3 (30.0) | 0 (0.0) | 2 (40.0) | 0 (0.0) | 5 (18.5) | 0 (0.0) | 11 (22.0) | 0 (0.0) |
| Anemia | 5 (62.5) | 5 (62.5) | 4 (40.0) | 2 (20.0) | 4 (80.0) | 2 (40.0) | 17 (63.0) | 11 (40.7) | 30 (60.0) | 20 (40.0) |
| Thrombocytopenia | 3 (37.5) | 1 (12.5) | 2 (20.0) | 0 (0.0) | 3 (60.0) | 2 (40.0) | 7 (25.9) | 4 (14.8) | 15 (30.0) | 7 (14.0) |
| Diarrhea | 3 (37.5) | 0 (0.0) | 3 (30.0) | 0 (0.0) | 4 (80.0) | 0 (0.0) | 12 (44.4) | 3 (11.1) | 22 (44.0) | 3 (6.0) |
| Constipation | 2 (25.0) | 0 (0.0) | 1 (10.0) | 0 (0.0) | 1 (20.0) | 0 (0.0) | 7 (25.9) | 0 (0.0) | 11 (22.0) | 0 (0.0) |
| Nausea | 3 (37.5) | 0 (0.0) | 1 (10.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 8 (29.6) | 0 (0.0) | 12 (24.0) | 0 (0.0) |
| Vomiting | 3 (37.5) | 0 (0.0) | 2 (20.0) | 0 (0.0) | 1 (20.0) | 0 (0.0) | 6 (22.2) | 1 (3.7) | 12 (24.0) | 1 (2.0) |
| Blood creatine phosphokinase increased* | 1 (12.5) | 0 (0.0) | 2 (20.0) | 2 (20.0) | 3 (60.0) | 1 (20.0) | 12 (44.4) | 6 (22.2) | 18 (36.0) | 9 (18.0) |
| Dysgeusia* | 3 (37.5) | 0 (0.0) | 4 (40.0) | 0 (0.0) | 3 (60.0) | 0 (0.0) | 9 (33.3) | 0 (0.0) | 19 (38.0) | 0 (0.0) |
| Alopecia* | 3 (37.5) | 0 (0.0) | 7 (70.0) | 0 (0.0) | 3 (60.0) | 0 (0.0) | 12 (44.4) | 0 (0.0) | 25 (50.0) | 0 (0.0) |
| . | Phase 1b dose-escalation phase, n (%) . | Phase 1b dose expansion phase and phase 2 stage 1. n (%) . | All patients (N = 50), n (%) . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 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 grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . |
| Total | 8 (100) | 8 (100) | 10 (100) | 8 (80) | 5 (100) | 4 (80) | 27 (100) | 19 (70.4) | 50 (100) | 39 (78) |
| Muscle spasms* | 3 (37.5) | 0 (0.0) | 6 (60.0) | 1 (10.0) | 4 (80.0) | 0 (0.0) | 18 (66.7) | 1 (3.7) | 31 (62.0) | 2 (4.0) |
| Myalgia* | 1 (12.5) | 0 (0.0) | 3 (30.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 10 (37.0) | 2 (7.4) | 14 (28.0) | 2 (4.0) |
| Fatigue | 6 (75.0) | 1 (12.5) | 3 (30.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 8 (29.6) | 0 (0.0) | 17 (34.0) | 1 (2.0) |
| Pyrexia | 2 (25.0) | 2 (25.0) | 2 (20.0) | 0 (0.0) | 2 (40.0) | 0 (0.0) | 9 (33.3) | 2 (7.4) | 15 (30.0) | 4 (8.0) |
| Cough | 1 (12.5) | 0 (0.0) | 3 (30.0) | 0 (0.0) | 2 (40.0) | 0 (0.0) | 5 (18.5) | 0 (0.0) | 11 (22.0) | 0 (0.0) |
| Anemia | 5 (62.5) | 5 (62.5) | 4 (40.0) | 2 (20.0) | 4 (80.0) | 2 (40.0) | 17 (63.0) | 11 (40.7) | 30 (60.0) | 20 (40.0) |
| Thrombocytopenia | 3 (37.5) | 1 (12.5) | 2 (20.0) | 0 (0.0) | 3 (60.0) | 2 (40.0) | 7 (25.9) | 4 (14.8) | 15 (30.0) | 7 (14.0) |
| Diarrhea | 3 (37.5) | 0 (0.0) | 3 (30.0) | 0 (0.0) | 4 (80.0) | 0 (0.0) | 12 (44.4) | 3 (11.1) | 22 (44.0) | 3 (6.0) |
| Constipation | 2 (25.0) | 0 (0.0) | 1 (10.0) | 0 (0.0) | 1 (20.0) | 0 (0.0) | 7 (25.9) | 0 (0.0) | 11 (22.0) | 0 (0.0) |
| Nausea | 3 (37.5) | 0 (0.0) | 1 (10.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 8 (29.6) | 0 (0.0) | 12 (24.0) | 0 (0.0) |
| Vomiting | 3 (37.5) | 0 (0.0) | 2 (20.0) | 0 (0.0) | 1 (20.0) | 0 (0.0) | 6 (22.2) | 1 (3.7) | 12 (24.0) | 1 (2.0) |
| Blood creatine phosphokinase increased* | 1 (12.5) | 0 (0.0) | 2 (20.0) | 2 (20.0) | 3 (60.0) | 1 (20.0) | 12 (44.4) | 6 (22.2) | 18 (36.0) | 9 (18.0) |
| Dysgeusia* | 3 (37.5) | 0 (0.0) | 4 (40.0) | 0 (0.0) | 3 (60.0) | 0 (0.0) | 9 (33.3) | 0 (0.0) | 19 (38.0) | 0 (0.0) |
| Alopecia* | 3 (37.5) | 0 (0.0) | 7 (70.0) | 0 (0.0) | 3 (60.0) | 0 (0.0) | 12 (44.4) | 0 (0.0) | 25 (50.0) | 0 (0.0) |
Associated with sonidegib treatment.