Table 3.
Treatment-emergent adverse events
| Adverse event | 4–32 mg Japanese cohort (n = 12) | 2–28 mg US cohort (n = 10) | 56–96 mg Japanese cohort (n = 6) | 48–80 mg US cohort (n = 11) | 160 mg Japanese cohort (n = 3) | 160 mg US cohort (n = 4) | 240 mg Japanese cohort (n = 6) | 240 mg US cohort (n = 9) | 320 mg US cohort (n = 8) | All (n = 69) |
|---|---|---|---|---|---|---|---|---|---|---|
| Diarrhoea | 6 | 5 | 4 (96 mg 1 G3) | 4 | 2 (1 G3) | 4 | 5 | 5 | 4 | 39 (56.5%) |
| Nausea | 6 | 6 | 1 | 6 | 3 | 2 | 6 | 4 | 5 | 39 (56.5%) |
| Fatigue | 5 | 7 (2, ≥G3) | 3 | 5 (1, ≥G3) | 1 | 4 | 2 | 5 (1, ≥G3) | 6 (1, G3) | 38 (55.1%) |
| Decreased appetite | 7 | 3 | 2 | 2 | 3 (1 G3) | 3 | 4 | 5 (1, ≥G3) | 5 | 34 (49.3%) |
| Vomiting | 4 | 4 | 1 | 3 | 2 | 2 | 3 | 3 | 4 | 26 (37.7%) |
| Rash | 3 | 2 | 4 | 4 (1, G3) | 2 | 0 | 5 | 0 | 3 | 23 (33.3%) |
| Stomatitis | 3 | 1 | 1 | 3 | 2 | 1 | 6 | 5 (1, G3) | 1 | 23 (33.3%) |
| Dysgeusia | 3 | 0 | 1 | 2 | 2 | 1 | 3 | 2 | 5 | 19 (27.5%) |
| Constipation | 3 | 3 | 1 | 0 | 1 | 2 | 1 | 1 | 1 | 13 (18.8%) |
| Dry mouth | 0 | 3 | 1 | 3 | 0 | 0 | 1 | 3 | 2 | 13 (18.8%) |
| Edema | 2 | 2 | 1 | 1 | 1 | 0 | 3 | 1 | 1 | 12 (17.4%) |
| Dyspnea | 2 | 2 | 0 | 1 | 1 | 0 | 0 | 3 | 2 | 12 (17.4%) |
| Hyperglycaemia | 0 | 0 | 2 (56 mg 1 G3, 96 mg 1 G3) | 2 | 1 (1 G3) | 1 | 1 (1 G4) | 2 | 3 | 12 (17.4%) |
| Cough | 1 | 2 | 1 | 3 | 2 | 0 | 1 | 0 | 1 | 11 (15.9%) |
| Back pain | 1 | 5 | 0 | 1 | 0 | 0 | 1 | 3 | 0 | 11 (15.9%) |
| Pyrexia | 0 | 1 | 0 | 2 | 1 | 0 | 2 | 2 | 2 | 10 (14.5%) |
| Abdominal pain | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 4 | 0 | 10 (14.5%) |
| Blood creatinine increased | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 2 | 2 | 7 (10.1%) |
| AST increased | 0 | 3 (1, ≥G3) | 1 | 1 | 0 | 0 | 0 | 2, ≥G3 | 0 | 7 (10.1%) |
| Dehydration | 0 | 0 | 0 | 1, G3 | 0 | 1 | 0 | 1 | 3 (1, G3) | 6 (8.7%) |
| Lung infection/ pneumonia | 0 | 1, G3 | 0 | 0 | 0 | 0 | 1 (1 G3) | 1 | 1, G3 | 4 (5.8%) |
Treatment-emergent AE (TEAE) shown here met either of the following criteria: (i) total incidence of ≥10% of the total number of subjects in both studies combined, and (ii) clinically significant or severe (≥G3) TEAE
A DLT regarding liver function was defined as follows: (i) grade 4 alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation; (ii) >5× upper limit of normal (ULN) ALT/AST elevation for more than 3 days in cases without liver metastasis; (iii) >5× ULN ALT/AST elevation with grade ≥2 hyperbilirubinemia; (iv) >5× ULN ALT/AST elevation for more than 3 days in cases with liver metastasis and whose baseline ALT/AST is ≤3× ULN; and (v) >8× ULN ALT/AST elevation for more than 3 days in cases with liver metastasis and whose baseline ALT/AST is >3× ULN and ≤5× ULN