Incidence of treatment-emergent AEs and selected laboratory abnormalities reported in 10% or more of patients
| Description . | Dosing regimen . | Overall N = 40 (%) . | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 50 mg bid 28 d (n = 5) . | 150 mg qd 28 d (n = 7) . | 100 mg bid 28 d (n = 7) . | 150 mg bid 21 d (n = 5) . | 300 mg qd 28 d (n = 4) . | 150 mg bid 28 d (n = 6) . | 200 mg bid 28 d (n = 3) . | 350 mg bid 28 d (n = 3) . | |||||||||||
| Grade . | Grade . | Grade . | Grade . | Grade . | Grade . | Grade . | Grade . | Grade . | ||||||||||
| Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | |
| Adverse event, n | ||||||||||||||||||
| Diarrhea | 1 | 0 | 4 | 2 | 3 | 3 | 2 | 0 | 1 | 0 | 3 | 1 | 2 | 1 | 0 | 0 | 16 (40.0%) | 7 (17.5%) |
| Nausea | 0 | 0 | 1 | 0 | 3 | 1 | 0 | 0 | 1 | 0 | 3 | 1 | 2 | 0 | 3 | 0 | 13 (32.5%) | 2 (5.0%) |
| Pyrexia | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 3 | 0 | 2 | 0 | 0 | 0 | 11 (27.5%) | 0 |
| Fatigue | 1 | 0 | 2 | 0 | 3 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 10 (25.0%) | 1 (2.5%) |
| Rash | 0 | 0 | 1 | 0 | 2 | 0 | 2 | 1 | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 9 (22.5%) | 1 (2.5%) |
| Anorexia | 0 | 0 | 1 | 0 | 3 | 3 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 2 | 1 | 8 (20.0%) | 6 (15.0%) |
| URI | 1 | 0 | 2 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 8 (20.0%) | 0 |
| Asthenia | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 7 (17.5%) | 0 |
| Constipation | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 1 | 0 | 6 (15.0%) | 0 |
| Headache | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 6 (15.0%) | 0 |
| Cough | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 5 (12.5%) | 0 |
| Pneumonia | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 5 (12.5%) | 5 (12.5%) |
| Vomiting | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 5 (12.5%) | 0 |
| Weight loss | 0 | 0 | 0 | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 5 (12.5%) | 2 (5.0%) |
| Dizziness | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 4 (10.0%) | 0 |
| Dyspnea | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 4 (10.0%) | 0 |
| Laboratory abnormality in ≥10% patients, n | ||||||||||||||||||
| AST, increased | 1 | 0 | 6 | 2 | 4 | 1 | 1 | 0 | 3 | 2 | 4 | 0 | 2 | 1 | 3 | 0 | 24 (60.0%) | 6 (15.0%) |
| ALT, increased | 0 | 0 | 5 | 2 | 3 | 2 | 2 | 1 | 3 | 2 | 4 | 0 | 1 | 1 | 2 | 0 | 20 (50.0%) | 8 (20.0%) |
| AP, increased | 2 | 0 | 5 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 14 (35.0%) | 0 |
| GGT, increased | 0 | 0 | 3 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 10 (25.0%) | 0 |
| Bilirubin, increased | 0 | 0 | 2 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 7 (17.5%) | 0 |
| Glucose, increased | 2 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 3 | 0 | 1 | 0 | 1 | 0 | 11 (27.5%) | 0 |
| Glucose, decreased | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 (12.5%) | 0 |
| BUN, increased | 2 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 7 (17.5%) | 0 |
| Cr, increased | 2 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 8 (20.0%) | 0 |
| ANC, decreased | 3 | 0 | 1 | 1 | 2 | 1 | 0 | 0 | 1 | 1 | 3 | 0 | 0 | 0 | 2 | 1 | 12 (30.0%) | 4 (10.0%) |
| Hgb, decreased | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 2 | 0 | 1 | 0 | 9 (22.5%) | 1 (2.5%) |
| Plts, decreased | 0 | 0 | 2 | 1 | 4 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 8 (20.0%) | 2 (5.0%) |
| Description . | Dosing regimen . | Overall N = 40 (%) . | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 50 mg bid 28 d (n = 5) . | 150 mg qd 28 d (n = 7) . | 100 mg bid 28 d (n = 7) . | 150 mg bid 21 d (n = 5) . | 300 mg qd 28 d (n = 4) . | 150 mg bid 28 d (n = 6) . | 200 mg bid 28 d (n = 3) . | 350 mg bid 28 d (n = 3) . | |||||||||||
| Grade . | Grade . | Grade . | Grade . | Grade . | Grade . | Grade . | Grade . | Grade . | ||||||||||
| Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | Any . | ≥3 . | |
| Adverse event, n | ||||||||||||||||||
| Diarrhea | 1 | 0 | 4 | 2 | 3 | 3 | 2 | 0 | 1 | 0 | 3 | 1 | 2 | 1 | 0 | 0 | 16 (40.0%) | 7 (17.5%) |
| Nausea | 0 | 0 | 1 | 0 | 3 | 1 | 0 | 0 | 1 | 0 | 3 | 1 | 2 | 0 | 3 | 0 | 13 (32.5%) | 2 (5.0%) |
| Pyrexia | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 3 | 0 | 2 | 0 | 0 | 0 | 11 (27.5%) | 0 |
| Fatigue | 1 | 0 | 2 | 0 | 3 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 10 (25.0%) | 1 (2.5%) |
| Rash | 0 | 0 | 1 | 0 | 2 | 0 | 2 | 1 | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 9 (22.5%) | 1 (2.5%) |
| Anorexia | 0 | 0 | 1 | 0 | 3 | 3 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 2 | 1 | 8 (20.0%) | 6 (15.0%) |
| URI | 1 | 0 | 2 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 8 (20.0%) | 0 |
| Asthenia | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 7 (17.5%) | 0 |
| Constipation | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 1 | 0 | 6 (15.0%) | 0 |
| Headache | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 6 (15.0%) | 0 |
| Cough | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 5 (12.5%) | 0 |
| Pneumonia | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 5 (12.5%) | 5 (12.5%) |
| Vomiting | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 5 (12.5%) | 0 |
| Weight loss | 0 | 0 | 0 | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 5 (12.5%) | 2 (5.0%) |
| Dizziness | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 4 (10.0%) | 0 |
| Dyspnea | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 4 (10.0%) | 0 |
| Laboratory abnormality in ≥10% patients, n | ||||||||||||||||||
| AST, increased | 1 | 0 | 6 | 2 | 4 | 1 | 1 | 0 | 3 | 2 | 4 | 0 | 2 | 1 | 3 | 0 | 24 (60.0%) | 6 (15.0%) |
| ALT, increased | 0 | 0 | 5 | 2 | 3 | 2 | 2 | 1 | 3 | 2 | 4 | 0 | 1 | 1 | 2 | 0 | 20 (50.0%) | 8 (20.0%) |
| AP, increased | 2 | 0 | 5 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 14 (35.0%) | 0 |
| GGT, increased | 0 | 0 | 3 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 10 (25.0%) | 0 |
| Bilirubin, increased | 0 | 0 | 2 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 7 (17.5%) | 0 |
| Glucose, increased | 2 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 3 | 0 | 1 | 0 | 1 | 0 | 11 (27.5%) | 0 |
| Glucose, decreased | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 (12.5%) | 0 |
| BUN, increased | 2 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 7 (17.5%) | 0 |
| Cr, increased | 2 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 8 (20.0%) | 0 |
| ANC, decreased | 3 | 0 | 1 | 1 | 2 | 1 | 0 | 0 | 1 | 1 | 3 | 0 | 0 | 0 | 2 | 1 | 12 (30.0%) | 4 (10.0%) |
| Hgb, decreased | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 2 | 0 | 1 | 0 | 9 (22.5%) | 1 (2.5%) |
| Plts, decreased | 0 | 0 | 2 | 1 | 4 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 8 (20.0%) | 2 (5.0%) |
ALT, alanine transaminase; ANC, absolute neutrophil count; AP, alkaline phosphatase; AST, aspartate transaminase; bid, twice daily; BUN, blood urea nitrogen; Cr, creatine; d, days; GGT, gamma-glutamyl transpeptidase; Hgb, hemoglobin; Plts, platelets; qd, daily; URI, upper respiratory infection.