Table 1.
TEAEs that occurred in ≥ 20% of patients (part 1, dose escalation and expansion)—safety set
| Grade | QD | BID | Total | ||||
|---|---|---|---|---|---|---|---|
| 20–420 mg | 560 mg | 240 mg | 360 mg | 480 mg | |||
| N = 27 | N = 43 | N = 12 | N = 19 | N = 40 | N = 141 | ||
| Diarrhea | Any | 18 (66.7) | 37 (86.0) | 10 (83.3) | 15 (78.9) | 38 (95.0) | 118 (83.7) |
| 1 | 7 (25.9) | 13 (30.2) | 6 (50.0) | 2 (10.5) | 6 (15.0) | 34 (24.1) | |
| 2 | 9 (33.3) | 16 (37.2) | 2 (16.7) | 11 (57.9) | 16 (40.0) | 54 (38.3) | |
| ≥ 3 | 2 (7.4) | 8 (18.6) | 2 (16.7) | 2 (10.5) | 16 (40.0) | 30 (21.3) | |
| Leukopenia | Any | 19 (70.4) | 35 (81.4) | 7 (58.3) | 17 (89.5) | 31 (77.5) | 109 (77.3) |
| 1 | 8 (29.6) | 5 (11.6) | 2 (16.7) | 5 (26.3) | 2 (5.0) | 22 (15.6) | |
| 2 | 10 (37.0) | 23 (53.5) | 5 (41.7) | 9 (47.4) | 19 (47.5) | 66 (46.8) | |
| ≥ 3 | 1 (3.7) | 7 (16.3) | 0 | 3 (15.8) | 10 (25.0) | 21 (14.9) | |
| Neutropenia | Any | 17 (63.0) | 37 (86.0) | 8 (66.7) | 16 (84.2) | 31 (77.5) | 109 (77.3) |
| 1 | 8 (29.6) | 5 (11.6) | 2 (16.7) | 5 (26.3) | 2 (5.0) | 22 (15.6) | |
| 2 | 5 (18.5) | 23 (53.5) | 5 (41.7) | 6 (31.6) | 15 (37.5) | 54 (38.3) | |
| ≥ 3 | 4 (14.8) | 9 (20.9) | 1 (8.3) | 5 (26.3) | 14 (35.0) | 33 (23.4) | |
| Vomiting | Any | 10 (37.0) | 31 (72.1) | 4 (33.3) | 7 (36.8) | 31 (77.5) | 83 (58.9) |
| 1 | 9 (33.3) | 24 (55.8) | 4 (33.3) | 3 (15.8) | 17 (42.5) | 57 (40.4) | |
| 2 | 0 | 3 (7.0) | 0 | 3 (15.8) | 8 (20.0) | 14 (9.9) | |
| ≥ 3 | 1 (3.7) | 4 (9.3) | 0 | 1 (5.3) | 6 (15.0) | 12 (8.5) | |
| Anemia | Any | 11 (40.7) | 27 (62.8) | 6 (50.0) | 12 (63.2) | 27 (67.5) | 83 (58.9) |
| 1 | 6 (22.2) | 11 (25.6) | 3 (25.0) | 7 (36.8) | 11 (27.5) | 38 (27.0) | |
| 2 | 4 (14.8) | 15 (34.9) | 3 (25.0) | 5 (26.3) | 9 (22.5) | 36 (25.5) | |
| ≥ 3 | 1 (3.7) | 1 (2.3) | 0 | 0 | 7 (17.5) | 9 (6.4) | |
| Creatinine increased | Any | 12 (44.4) | 27 (62.8) | 4 (33.3) | 14 (73.7) | 21 (52.5) | 78 (55.3) |
| 1 | 11 (40.7) | 23 (53.5) | 3 (25.0) | 11 (57.9) | 15 (37.5) | 63 (44.7) | |
| 2 | 1 (3.7) | 3 (7.0) | 1 (8.3) | 3 (15.8) | 6 (15.0) | 14 (9.9) | |
| ≥ 3 | 0 | 1 (2.3) | 0 | 0 | 0 | 1 (0.7) | |
| Nausea | Any | 10 (37.0) | 22 (51.2) | 3 (25.0) | 7 (36.8) | 24 (60.0) | 66 (46.8) |
| 1 | 10 (37.0) | 21 (48.8) | 3 (25.0) | 7 (36.8) | 16 (40.0) | 57 (40.4) | |
| 2 | 0 | 1 (2.3) | 0 | 0 | 8 (20.0) | 9 (6.4) | |
| ≥ 3 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Hypertriglyceridemia | Any | 6 (22.2) | 25 (58.1) | 4 (33.3) | 10 (52.6) | 14 (35.0) | 59 (41.8) |
| 1 | 1 (3.7) | 20 (46.5) | 2 (16.7) | 6 (31.6) | 9 (22.5) | 38 (27.0) | |
| 2 | 4 (14.8) | 3 (7.0) | 2 (16.7) | 2 (10.5) | 3 (7.5) | 14 (9.9) | |
| ≥ 3 | 1 (3.7) | 2 (4.7) | 0 | 2 (10.5) | 2 (5.0) | 7 (5.0) | |
| Thrombocytopenia | Any | 4 (14.8) | 21 (48.8) | 3 (25.0) | 6 (31.6) | 21 (52.5) | 55 (39.0) |
| 1 | 3 (11.1) | 15 (34.9) | 2 (16.7) | 3 (15.8) | 11 (27.5) | 34 (24.1) | |
| 2 | 0 | 4 (9.3) | 0 | 2 (10.5) | 4 (10.0) | 10 (7.1) | |
| ≥ 3 | 1 (3.7) | 2 (4.7) | 1 (8.3) | 1 (5.3) | 6 (15.0) | 11 (7.8) | |
| Elevated ALT | Any | 10 (37.0) | 17 (39.5) | 5 (41.7) | 6 (31.6) | 16 (40.0) | 54 (38.3) |
| 1 | 9 (33.3) | 15 (34.9) | 3 (25.0) | 6 (31.6) | 11 (27.5) | 44 (31.2) | |
| 2 | 1 (3.7) | 2 (4.7) | 1 (8.3) | 0 | 2 (5.0) | 6 (4.3) | |
| ≥ 3 | 0 | 0 | 1 (8.3) | 0 | 3 (7.5) | 4 (2.8) | |
| Elevated AST | Any | 9 (33.3) | 15 (34.9) | 4 (33.3) | 9 (47.4) | 15 (37.5) | 52 (36.9) |
| 1 | 9 (33.3) | 13 (30.2) | 2 (16.7) | 8 (42.1) | 9 (22.5) | 41 (29.1) | |
| 2 | 0 | 2 (4.7) | 1 (8.3) | 1 (5.3) | 2 (5.0) | 6 (4.3) | |
| ≥ 3 | 0 | 0 | 1 (8.3) | 0 | 4 (10.0) | 5 (3.5) | |
| Hypokalemia | Any | 2 (7.4) | 11 (25.6) | 3 (25.0) | 8 (42.1) | 19 (47.5) | 43 (30.5) |
| 1 | 2 (7.4) | 11 (25.6) | 3 (25.0) | 7 (36.8) | 12 (30.0) | 35 (24.8) | |
| 2 | 0 | 0 | 0 | 0 | 2 (5.0) | 2 (1.4) | |
| ≥ 3 | 0 | 0 | 0 | 1 (5.3) | 5 (12.5) | 6 (4.3) | |
| Abdominal pain | Any | 8 (29.6) | 15 (34.9) | 0 | 3 (15.8) | 13 (32.5) | 39 (27.7) |
| 1 | 8 (29.6) | 14 (32.6) | 0 | 2 (10.5) | 10 (25.0) | 34 (24.1) | |
| 2 | 0 | 1 (2.3) | 0 | 1 (5.3) | 3 (7.5) | 5 (3.5) | |
| ≥ 3 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Hypercholesteremia | Any | 2 (7.4) | 16 (37.2) | 2 (16.7) | 6 (31.6) | 12 (30.0) | 38 (27.0) |
| 1 | 1 (3.7) | 15 (34.9) | 1 (8.3) | 5 (26.3) | 11 (27.5) | 33 (23.4) | |
| 2 | 1 (3.7) | 1 (2.3) | 1 (8.3) | 0 | 1 (2.5) | 4 (2.8) | |
| ≥ 3 | 0 | 0 | 0 | 1 (5.3) | 0 | 1 (0.7) | |
| Hypoalbuminemia | Any | 1 (3.7) | 10 (23.3) | 4 (33.3) | 7 (36.8) | 13 (32.5) | 35 (24.8) |
| 1 | 1 (3.7) | 9 (20.9) | 4 (33.3) | 7 (36.8) | 12 (30.0) | 33 (23.4) | |
| 2 | 0 | 1 (2.3) | 0 | 0 | 1 (2.5) | 2 (1.4) | |
| ≥ 3 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Urinary tract infection | Any | 3 (11.1) | 9 (20.9) | 2 (16.7) | 7 (36.8) | 14 (35.0) | 35 (24.8) |
| 1 | 0 | 5 (11.6) | 2 (16.7) | 5 (26.3) | 11 (27.5) | 23 (16.3) | |
| 2 | 3 (11.1) | 4 (9.3) | 0 | 2 (10.5) | 3 (7.5) | 12 (8.5) | |
| ≥ 3 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Weight decrease | Any | 4 (14.8) | 7 (16.3) | 1 (8.3) | 7 (36.8) | 13 (32.5) | 32 (22.7) |
| 1 | 0 | 6 (14.0) | 1 (8.3) | 5 (26.3) | 10 (25.0) | 22 (15.6) | |
| 2 | 3 (11.1) | 1 (2.3) | 0 | 1 (5.3) | 3 (7.5) | 8 (5.7) | |
| ≥ 3 | 1 (3.7) | 0 | 0 | 1 (5.3) | 0 | 2 (1.4) | |
| Hyperuricemia | Any | 6 (22.2) | 13 (30.2) | 1 (8.3) | 3 (15.8) | 8 (20.0) | 31 (22.0) |
| 1 | 6 (22.2) | 13 (30.2) | 1 (8.3) | 3 (15.8) | 8 (20.0) | 31 (22.0) | |
| 2 | 0 | 0 | 0 | 0 | 0 | 0 | |
| ≥ 3 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Epigastric pain | Any | 3 (11.1) | 9 (20.9) | 2 (16.7) | 3 (15.8) | 12 (30.0) | 29 (20.6) |
| 1 | 3 (11.1) | 8 (18.6) | 2 (16.7) | 3 (15.8) | 9 (22.5) | 25 (17.7) | |
| 2 | 0 | 1 (2.3) | 0 | 0 | 3 (7.5) | 4 (2.8) | |
| ≥ 3 | 0 | 0 | 0 | 0 | 0 | 0 | |
Data are presented as number of patients (incidence). ALT alanine aminotransferase; AST aspartate aminotransferase; BID twice-daily; QD once-daily; TEAEs treatment-emergent adverse events