Table 2.
Adverse events.
| Dose-escalation phase Ib | Dose-expansion phase II | |||||
|---|---|---|---|---|---|---|
| 28-day schedule | 21-day schedule | 28-day schedulea | ||||
| N = 29 | N = 32 | N = 41 | ||||
| Any grade | Grade 3–4 | Any grade | Grade 3–4 | Any grade | Grade 3–4 | |
| n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | |
| Any AE | 29 (100) | 26 (89.7) | 32 (100) | 24 (75.0) | 41 (100) | 38 (92.7) |
| Serious AEs | 16 (55.2) | 14 (48.3) | 14 (43.8) | 11 (34.4) | 22 (53.7) | 18 (43.9) |
| AEs leading to discontinuationb | 10 (34.5) | 7 (24.1) | 3 (9.4) | 3 (9.4) | 13 (31.7) | 11 (26.8) |
| AEs requiring dose interruption and/or changes | 21 (72.4) | 21 (72.4) | 23 (71.9) | 16 (50.0) | 31 (75.6) | 25 (61.0) |
| AEs in >20% of patients in either group | ||||||
| Blood CPK increase | 20 (69.0) | 5 (17.2) | 13 (40.6) | 5 (15.6) | 24 (58.5) | 10 (24.4) |
| Diarrhea | 14 (48.3) | 0 | 19 (59.4) | 1 (3.1) | 21 (51.2) | 3 (7.3) |
| Nausea | 15 (51.7) | 2 (6.9) | 12 (37.5) | 2 (6.3) | 22 (53.7) | 1 (2.4) |
| Fatigue | 10 (34.5) | 0 | 16 (50.0) | 1 (3.1) | 15 (36.6) | 2 (4.9) |
| Vomiting | 14 (48.3) | 3 (10.3) | 11 (34.4) | 0 | 14 (34.1) | 2 (4.9) |
| Peripheral edema | 14 (48.3) | 1 (3.4) | 7 (21.9) | 0 | 18 (43.9) | 2 (4.9) |
| Anemia | 13 (44.8) | 2 (6.9) | 8 (25.0) | 1 (3.1) | 10 (24.4) | 0 |
| AST increase | 12 (41.4) | 4 (13.8) | 9 (28.1) | 2 (6.3) | 20 (48.8) | 9 (22.0) |
| Rash | 9 (31.0) | 3 (10.3) | 11 (34.4) | 1 (3.1) | 6 (14.6) | 0 |
| Acneiform dermatitis | 9 (31.0) | 1 (3.4) | 8 (25.0) | 0 | 18 (43.9) | 3 (7.3) |
| ALT increase | 9 (31.0) | 4 (13.8) | 7 (21.9) | 2 (6.3) | 18 (43.9) | 10 (24.4) |
| Neutropenia | 7 (24.1) | 2 (6.9) | 8 (25.0) | 6 (18.8) | 5 (12.2) | 0 |
| Hypoalbuminemia | 11 (37.9) | 2 (6.9) | 3 (9.4) | 0 | 6 (14.6) | 1 (2.4) |
| Constipation | 9 (31.0) | 1 (3.4) | 5 (15.6) | 1 (3.1) | 8 (19.5) | 1 (2.4) |
| Pyrexia | 5 (17.2) | 0 | 9 (28.1) | 3 (9.4) | 11 (26.8) | 1 (2.4) |
| Hypomagnesemia | 9 (31.0) | 0 | 4 (12.5) | 0 | 3 (7.3) | 0 |
| Hypokalemia | 4 (13.8) | 2 (6.9) | 0 | 0 | 9 (22.0) | 2 (4.9) |
Abbreviations: N, total number of patients in treatment group; n, number of patients with the event.
aBinimetinib twice daily on a continuous dosing schedule plus ribociclib once daily for 21 consecutive days followed by a 7-day planned break.
bAEs associated with discontinuation although may not be primary reason for discontinuation.