Overview of AEs
| Category, n (%) . | Ruxolitinib plus siremadlin 20 mg (n = 7) . | Ruxolitinib plus siremadlin 30 mg (n = 10) . | Ruxolitinib plus siremadlin 40 mg (n = 6) . | Ruxolitinib plus siremadlin total (N = 23) . | ||||
|---|---|---|---|---|---|---|---|---|
| All grades . | Grade ≥3 . | All grades . | Grade ≥3 . | All grades . | Grade ≥3 . | All grades . | Grade ≥3 . | |
| AEs | 7 (100) | 5 (71.4) | 10 (100) | 10 (100) | 6 (100) | 6 (100) | 23 (100) | 21 (91.3) |
| Study treatment related | 7 (100) | 4 (57.1) | 10 (100) | 10 (100) | 6 (100) | 6 (100) | 23 (100) | 20 (87.0) |
| Ruxolitinib related | 3 (42.9) | 2 (28.6) | 8 (80.0) | 7 (70.0) | 6 (100) | 6 (100) | 17 (73.9) | 15 (65.2) |
| Siremadlin related | 7 (100) | 3 (42.9) | 10 (100) | 10 (100) | 6 (100) | 6 (100) | 23 (100) | 19 (82.6) |
| SAEs | 1 (14.3) | 1 (14.3) | 3 (30.0) | 3 (30.0) | 4 (66.7) | 4 (66.7) | 8 (34.8) | 8 (34.8) |
| Study treatment related | 0 | 0 | 2 (20.0) | 2 (20.0) | 2 (33.3) | 2 (33.3) | 4 (17.4) | 4 (17.4) |
| Fatal SAEs | 0 | 0 | 0 | 0 | 2 (33.3) | 2 (33.3) | 2 (8.7) | 2 (8.7) |
| Study treatment related | 0 | 0 | 0 | 0 | 1 (16.7) | 1 (16.7) | 1 (4.3) | 1 (4.3) |
| AEs leading to discontinuation | 3 (42.9) | 2 (28.6) | 6 (60.0) | 5 (50.0) | 2 (33.3) | 2 (33.3) | 11 (47.8) | 9 (39.1) |
| Study treatment related | 2 (28.6) | 1 (14.3) | 5 (50.0) | 5 (50.0) | 2 (33.3) | 2 (33.3) | 9 (39.1) | 8 (34.8) |
| AEs leading to dose adjustment/interruption | 4 (57.1) | 4 (57.1) | 8 (80.0) | 7 (70.0) | 6 (100) | 6 (100) | 18 (78.3) | 17 (73.9) |
| Most frequent AEs by PT (≥20% in any arm) | ||||||||
| Anemia | 3 (42.9) | 2 (28.6) | 7 (70.0) | 7 (70.0) | 5 (83.3) | 5 (83.3) | 15 (65.2) | 14 (60.9) |
| Thrombocytopenia | 1 (14.3) | 1 (14.3) | 7 (70.0) | 5 (50.0) | 6 (100.0) | 5 (83.3) | 14 (60.9) | 11 (47.8) |
| Nausea | 6 (85.7) | 0 | 4 (40.0) | 0 | 3 (50.0) | 0 | 13 (56.5) | 0 |
| Neutropenia | 0 | 0 | 8 (80.0) | 8 (80.0) | 3 (50.0) | 3 (50.0) | 11 (47.8) | 11 (47.8) |
| Fatigue | 5 (71.4) | 1 (14.3) | 1 (10.0) | 0 | 2 (33.3) | 0 | 8 (34.8) | 1 (4.3) |
| Diarrhea | 3 (42.9) | 1 (14.3) | 2 (20.0) | 0 | 0 | 0 | 5 (21.7) | 1 (4.3) |
| Pyrexia | 0 | 0 | 3 (30.0) | 0 | 2 (33.3) | 0 | 5 (21.7) | 0 |
| Headache | 3 (42.9) | 0 | 1 (10.0) | 0 | 0 | 0 | 4 (17.4) | 0 |
| Hyperuricemia | 1 (14.3) | 0 | 2 (20.0) | 1 (10.0) | 1 (16.7) | 0 | 4 (17.4) | 1 (4.3) |
| Insomnia | 0 | 0 | 0 | 0 | 2 (33.3) | 0 | 2 (8.7) | 0 |
| Constipation | 1 (14.3) | 0 | 2 (20.0) | 0 | 1 (16.7) | 0 | 4 (17.4) | 0 |
| Hypertension | 4 (57.1) | 4 (57.1) | 0 | 0 | 0 | 0 | 4 (17.4) | 4 (17.4) |
| Vomiting | 1 (14.3) | 0 | 2 (20.0) | 0 | 0 | 0 | 3 (13.0) | 0 |
| COVID-19 | 0 | 0 | 2 (20.0) | 0 | 2 (33.3) | 1 (16.7) | 4 (17.4) | 1 (4.3) |
| Decreased appetite | 3 (42.9) | 0 | 0 | 0 | 0 | 0 | 3 (13.0) | 0 |
| Dysgeusia | 0 | 0 | 0 | 0 | 2 (33.3) | 0 | 2 (8.7) | 0 |
| Category, n (%) . | Ruxolitinib plus siremadlin 20 mg (n = 7) . | Ruxolitinib plus siremadlin 30 mg (n = 10) . | Ruxolitinib plus siremadlin 40 mg (n = 6) . | Ruxolitinib plus siremadlin total (N = 23) . | ||||
|---|---|---|---|---|---|---|---|---|
| All grades . | Grade ≥3 . | All grades . | Grade ≥3 . | All grades . | Grade ≥3 . | All grades . | Grade ≥3 . | |
| AEs | 7 (100) | 5 (71.4) | 10 (100) | 10 (100) | 6 (100) | 6 (100) | 23 (100) | 21 (91.3) |
| Study treatment related | 7 (100) | 4 (57.1) | 10 (100) | 10 (100) | 6 (100) | 6 (100) | 23 (100) | 20 (87.0) |
| Ruxolitinib related | 3 (42.9) | 2 (28.6) | 8 (80.0) | 7 (70.0) | 6 (100) | 6 (100) | 17 (73.9) | 15 (65.2) |
| Siremadlin related | 7 (100) | 3 (42.9) | 10 (100) | 10 (100) | 6 (100) | 6 (100) | 23 (100) | 19 (82.6) |
| SAEs | 1 (14.3) | 1 (14.3) | 3 (30.0) | 3 (30.0) | 4 (66.7) | 4 (66.7) | 8 (34.8) | 8 (34.8) |
| Study treatment related | 0 | 0 | 2 (20.0) | 2 (20.0) | 2 (33.3) | 2 (33.3) | 4 (17.4) | 4 (17.4) |
| Fatal SAEs | 0 | 0 | 0 | 0 | 2 (33.3) | 2 (33.3) | 2 (8.7) | 2 (8.7) |
| Study treatment related | 0 | 0 | 0 | 0 | 1 (16.7) | 1 (16.7) | 1 (4.3) | 1 (4.3) |
| AEs leading to discontinuation | 3 (42.9) | 2 (28.6) | 6 (60.0) | 5 (50.0) | 2 (33.3) | 2 (33.3) | 11 (47.8) | 9 (39.1) |
| Study treatment related | 2 (28.6) | 1 (14.3) | 5 (50.0) | 5 (50.0) | 2 (33.3) | 2 (33.3) | 9 (39.1) | 8 (34.8) |
| AEs leading to dose adjustment/interruption | 4 (57.1) | 4 (57.1) | 8 (80.0) | 7 (70.0) | 6 (100) | 6 (100) | 18 (78.3) | 17 (73.9) |
| Most frequent AEs by PT (≥20% in any arm) | ||||||||
| Anemia | 3 (42.9) | 2 (28.6) | 7 (70.0) | 7 (70.0) | 5 (83.3) | 5 (83.3) | 15 (65.2) | 14 (60.9) |
| Thrombocytopenia | 1 (14.3) | 1 (14.3) | 7 (70.0) | 5 (50.0) | 6 (100.0) | 5 (83.3) | 14 (60.9) | 11 (47.8) |
| Nausea | 6 (85.7) | 0 | 4 (40.0) | 0 | 3 (50.0) | 0 | 13 (56.5) | 0 |
| Neutropenia | 0 | 0 | 8 (80.0) | 8 (80.0) | 3 (50.0) | 3 (50.0) | 11 (47.8) | 11 (47.8) |
| Fatigue | 5 (71.4) | 1 (14.3) | 1 (10.0) | 0 | 2 (33.3) | 0 | 8 (34.8) | 1 (4.3) |
| Diarrhea | 3 (42.9) | 1 (14.3) | 2 (20.0) | 0 | 0 | 0 | 5 (21.7) | 1 (4.3) |
| Pyrexia | 0 | 0 | 3 (30.0) | 0 | 2 (33.3) | 0 | 5 (21.7) | 0 |
| Headache | 3 (42.9) | 0 | 1 (10.0) | 0 | 0 | 0 | 4 (17.4) | 0 |
| Hyperuricemia | 1 (14.3) | 0 | 2 (20.0) | 1 (10.0) | 1 (16.7) | 0 | 4 (17.4) | 1 (4.3) |
| Insomnia | 0 | 0 | 0 | 0 | 2 (33.3) | 0 | 2 (8.7) | 0 |
| Constipation | 1 (14.3) | 0 | 2 (20.0) | 0 | 1 (16.7) | 0 | 4 (17.4) | 0 |
| Hypertension | 4 (57.1) | 4 (57.1) | 0 | 0 | 0 | 0 | 4 (17.4) | 4 (17.4) |
| Vomiting | 1 (14.3) | 0 | 2 (20.0) | 0 | 0 | 0 | 3 (13.0) | 0 |
| COVID-19 | 0 | 0 | 2 (20.0) | 0 | 2 (33.3) | 1 (16.7) | 4 (17.4) | 1 (4.3) |
| Decreased appetite | 3 (42.9) | 0 | 0 | 0 | 0 | 0 | 3 (13.0) | 0 |
| Dysgeusia | 0 | 0 | 0 | 0 | 2 (33.3) | 0 | 2 (8.7) | 0 |
Numbers (n) represent counts of patients. A patient with multiple severity grades for an AE is counted only under the maximum grade.
PT, preferred term; SAE, serious AE.