Table 3.
Treatment-emergent AEs occurring in ≥10% of all patients in futibatinib studies.
| TEAE (%) | Phase I dose escalation combined QD cohort61 (n = 44) |
Phase I dose expansion 20 mg QD cohort67 (n = 170) |
Japanese phase I expansion/escalation QD cohort (n=43) | Phase II iCCA 20 mg QD48 (n = 103) |
||||
|---|---|---|---|---|---|---|---|---|
| Any-grade | Grade 3a | Any-grade | Grade ≥3b | Any-grade | Grade ≥3 | Any-grade | Grade ≥3c | |
| Hyperphosphatemia | 68 | 16 | 81 | 22.4 | 100 | 5 | 85 | 30 |
| Constipation | 41 | 2 | 32 | 1.2 | 40 | 0 | 39 | 0 |
| Diarrhea | 34 | 2 | 33 | <1 | 30 | 0 | 36 | 1 |
| Nausea | 30 | 5 | 28 | 0 | 30 | 0 | 24 | 2 |
| ALT increased | 25 | 7 | 24 | 10 | 21 | 0 | 17 | 6 |
| AST increased | 25 | 5 | 24 | 5 | 21 | 2 | 25 | 10 |
| Dry mouth | 25 | 0 | 18 | 0 | - | - | 35 | 0 |
| Vomiting | 25 | 5 | 25 | 1 | 23 | 2 | 19 | 1 |
| Anemia | 20 | 5 | 14 | 5 | 19 | 12 | 16 | 5 |
| Asthenia | 20 | 0 | 16 | 4 | - | - | - | - |
| Stomatitis | 20 | 2 | 15 | 3 | 16 | 0 | 24 | 6 |
| Decreased appetite | 16 | 0 | 19 | 2 | 58 | 5 | 23 | 3 |
| Fatigue | 16 | 2 | 25 | 5 | 9 | 0 | 34 | 8 |
| Abdominal pain | 14 | 2 | 19 | 3 | - | - | 21 | 3 |
| Alopecia | 14 | 0 | 19 | 0 | - | - | 34 | 0 |
| Dry skin | 14 | 0 | 13 | 0 | 14 | 0 | 29 | 0 |
| Back pain | 11 | 0 | - | - | - | - | 17 | 2 |
| Cough | 11 | 0 | - | - | - | - | - | - |
| Dry eye | 11 | 0 | - | - | - | - | 21 | 1 |
| PPE syndrome | - | - | 13 | 4 | - | - | 21 | 5 |
| Increased blood creatinine | - | - | 12 | 0 | 16 | 2 | 15 | 0 |
| Arthralgia | - | - | 11 | 0 | 5 | 0 | 22 | 0 |
| Hypercalcemia | - | - | 11 | 1 | - | - | 16 | 2 |
| Dysgeusia | - | - | 11 | 0 | 14 | 9 | 20 | 0 |
| Decreased weight | - | - | 10 | <1 | 12 | 9 | 18 | 4 |
| Urinary-tract infection | - | - | - | - | - | - | 19 | 3 |
| Hyponatremia | - | - | - | - | 14 | 0 | 16 | 11 |
| Nail disorder | - | - | - | - | - | - | 16 | 0 |
| Onycholysis | - | - | - | - | - | - | 16 | 0 |
| Muscle spasms | - | - | - | - | - | - | 15 | 1 |
| Myalgia | - | - | - | - | - | - | 15 | 0 |
| Onychomadesis | - | - | - | - | - | - | 15 | 1 |
| Nail discoloration | - | - | - | - | - | - | 14 | 0 |
| Peripheral edema | - | - | - | - | 14 | 2 | 14 | 0 |
| Pyrexia | - | - | - | - | 7 | 0 | 14 | 0 |
| Blood alkaline phosphatase increase | - | - | - | - | - | - | 13 | 3 |
| Hypophosphatasemia | - | - | - | - | 7 | 5 | 13 | 5 |
| Dizziness | - | - | - | - | - | - | 11 | 1 |
| Thrombocytopenia | - | - | - | - | - | - | 11 | 2 |
| Blood creatine phosphokinase increase | - | - | - | - | 16 | 2 | 10 | 3 |
| Oropharyngeal pain | - | - | - | - | - | - | 10 | 0 |
| Peripheral sensory neuropathy | - | - | - | - | - | - | 10 | 1 |
| Hypoalbuminemia | - | - | - | 14 | 9 | - | - | - |
| Insomnia | - | - | - | 12 | 0 | - | - | - |
| Tumor pain | - | - | - | 14 | 0 | - | - | - |
Dashed lines (-) indicate the TEAE was reported in fewer than 10% of patients.
aNone of the TEAEs reported in this table were grade 4 or 5. Among patients treated with the once daily dose in this study, 3 patients had grade 4 TEAEs (one of which was considered treatment-related [increased creating phosphokinase]) and 4 patients had grade 5 events (none of which were considered treatment related).
bAmong any-grade TEAEs reported in >10% of patients, there was one grade 4 event (increased ALT) and there were no grade 5 events. Overall, 9 patients had grade TEAEs, one of which was considered treatment-related (increased gamma glutamyltransferase). None of the grade 5 TEAEs (n = 16) were considered treatment related.
cAmong any-grade TEAEs reported in ≥10% of patients, 4 grade 4 events were reported (1 patient each of increased ALT, hypercalcemia, hyponatremia, and hypophosphatasemia), and 1 grade 5 event was reported (decreased appetite). Overall, 6 patients had grade 4 TEAEs, 1 of which was considered treatment-related (increased ALT). None of the grade 5 TEAEs (n = 5) were treatment related.
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartine aminotransferase; iCCA, intrahepatic cholangiocarcinoma; PPE, Palmar–plantar erythrodysesthesia syndrome; QD, once daily; TEAEs, treatment-emergent adverse events.