Baseline patient characteristics
| Demographic variable/disease history . | Phase 1b dose-escalation phase . | Phase 1b dose expansion phase and phase 2 stage 1 . | . | ||
|---|---|---|---|---|---|
| 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) . | |
| Age, median (range), y | 73.0 (63-77) | 58.5 (42-75) | 71.0 (42-74) | 69.0 (44-83) | 68.5 (42-83) |
| Age ≥60 y, n (%) | 8 (100) | 5 (50.0) | 4 (80.0) | 21 (77.8) | 38 (76.0) |
| Male, n (%) | 7 (87.5) | 5 (50.0) | 4 (80.0) | 19 (70.4) | 35 (70.0) |
| ECOG PS, n (%) | |||||
| 0 | 1 (12.5) | 2 (20.0) | 3 (60.0) | 13 (48.1) | 19 (38.0) |
| 1 | 6 (75.0) | 8 (80.0) | 2 (40.0) | 14 (51.9) | 30 (60.0) |
| 2 | 1 (12.5) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (2.0) |
| Diagnosis of disease, n (%) | |||||
| PMF | 1 (12.5) | 7 (70.0) | 2 (40.0) | 16 (59.3) | 26 (52.0) |
| Post-PV MF | 5 (62.5) | 2 (20.0) | 1 (20.0) | 4 (14.8) | 12 (24.0) |
| Post-ET MF | 2 (25.0) | 1 (10.0) | 2 (40.0) | 7 (25.9) | 12 (24.0) |
| Spleen parameters | |||||
| Spleen size measured by palpation, mean ± SD, cm | 17.4 (8.78) | 13.1 (10.14) | 15.5 (5.02) | 11.6 (7.01) | 13.2 (7.93) |
| Spleen volume measured by MRI/CT scan, mean ± SD, cm3 | — | — | — | 1953.6 (932.03) | — |
| BM fibrosis grade (most recent diagnosis result prior to study entry), n (%) | |||||
| 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (7.4) | 2 (4.0) |
| 1 | 0 (0.0) | 1 (10.0) | 0 (0.0) | 3 (11.1) | |
| 2 | 5 (62.5) | 5 (50.0) | 2 (40.0) | 9 (33.3) | 21 (42.0) |
| 3 | 3 (37.5) | 3 (30.0) | 3 (60.0) | 11 (40.7) | 20 (40.0) |
| Missing | 0 (0.0) | 1 (10.0) | 0 (0.0) | 2 (7.4) | 3 (6.0) |
| IPSS risk factor at time of study entry, n (%) | |||||
| Low | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Intermediate-1 | 1 (12.5) | 5 (50.0) | 0 (0.0) | 5 (18.5) | 11 (22.0) |
| Intermediate-2 | 1 (12.5) | 2 (20.0) | 3 (60.0) | 4 (14.8) | 10 (20.0) |
| High | 6 (75.0) | 3 (30.0) | 2 (40.0) | 18 (66.7) | 29 (58.0) |
| JAK2 V617F allele burden,*n (%) | |||||
| Positive | 8 (100.0) | 8 (80.0) | 5 (100.0) | 23 (85.2) | 44 (88) |
| Negative | 0 (0.0) | 2 (20.0) | 0 (0.0) | 4 (14.8) | 6 (12) |
| Demographic variable/disease history . | Phase 1b dose-escalation phase . | Phase 1b dose expansion phase and phase 2 stage 1 . | . | ||
|---|---|---|---|---|---|
| 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) . | |
| Age, median (range), y | 73.0 (63-77) | 58.5 (42-75) | 71.0 (42-74) | 69.0 (44-83) | 68.5 (42-83) |
| Age ≥60 y, n (%) | 8 (100) | 5 (50.0) | 4 (80.0) | 21 (77.8) | 38 (76.0) |
| Male, n (%) | 7 (87.5) | 5 (50.0) | 4 (80.0) | 19 (70.4) | 35 (70.0) |
| ECOG PS, n (%) | |||||
| 0 | 1 (12.5) | 2 (20.0) | 3 (60.0) | 13 (48.1) | 19 (38.0) |
| 1 | 6 (75.0) | 8 (80.0) | 2 (40.0) | 14 (51.9) | 30 (60.0) |
| 2 | 1 (12.5) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (2.0) |
| Diagnosis of disease, n (%) | |||||
| PMF | 1 (12.5) | 7 (70.0) | 2 (40.0) | 16 (59.3) | 26 (52.0) |
| Post-PV MF | 5 (62.5) | 2 (20.0) | 1 (20.0) | 4 (14.8) | 12 (24.0) |
| Post-ET MF | 2 (25.0) | 1 (10.0) | 2 (40.0) | 7 (25.9) | 12 (24.0) |
| Spleen parameters | |||||
| Spleen size measured by palpation, mean ± SD, cm | 17.4 (8.78) | 13.1 (10.14) | 15.5 (5.02) | 11.6 (7.01) | 13.2 (7.93) |
| Spleen volume measured by MRI/CT scan, mean ± SD, cm3 | — | — | — | 1953.6 (932.03) | — |
| BM fibrosis grade (most recent diagnosis result prior to study entry), n (%) | |||||
| 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (7.4) | 2 (4.0) |
| 1 | 0 (0.0) | 1 (10.0) | 0 (0.0) | 3 (11.1) | |
| 2 | 5 (62.5) | 5 (50.0) | 2 (40.0) | 9 (33.3) | 21 (42.0) |
| 3 | 3 (37.5) | 3 (30.0) | 3 (60.0) | 11 (40.7) | 20 (40.0) |
| Missing | 0 (0.0) | 1 (10.0) | 0 (0.0) | 2 (7.4) | 3 (6.0) |
| IPSS risk factor at time of study entry, n (%) | |||||
| Low | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Intermediate-1 | 1 (12.5) | 5 (50.0) | 0 (0.0) | 5 (18.5) | 11 (22.0) |
| Intermediate-2 | 1 (12.5) | 2 (20.0) | 3 (60.0) | 4 (14.8) | 10 (20.0) |
| High | 6 (75.0) | 3 (30.0) | 2 (40.0) | 18 (66.7) | 29 (58.0) |
| JAK2 V617F allele burden,*n (%) | |||||
| Positive | 8 (100.0) | 8 (80.0) | 5 (100.0) | 23 (85.2) | 44 (88) |
| Negative | 0 (0.0) | 2 (20.0) | 0 (0.0) | 4 (14.8) | 6 (12) |
—, not available; ECOG PS, Eastern Cooperative Oncology Group Performance Status; IPSS, International Prognostic Scoring System; LLOQ, lower limit of quantitation; SD, standard deviation.
The interpretation of mutation is based on the mean allele burden value compared with LLOQ, which is equal to 5.0 in this study. If ≥LLOQ, then it is positive. Any value <LLOQ will be considered as mutation negative.