Hepatocellular Carcinoma (HCC)
Conditions
Keywords
Liver cancer, FGF19 gene amplification, FGF19 overexpression, FGF19 upregulation, Cyclin D1 (CCND1) gene amplification, Cyclin D1 (CCND1) copy number gain, BLU-554, FGFR4, Hepatocellular carcinoma, Liver Disease, Liver Neoplasms
Brief summary
This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of fisogatinib (formerly known as BLU- 554) administered orally in patients with FGF19 IHC+ hepatocellular carcinoma (HCC). The study consists of 3 parts, a dose-escalation part (Part 1), an expansion part (Part 2) exploring a once daily (qd) dosing schedule at the recommended Phase 2 dose (RP2D), and a Part 3 expansion of the qd dosing schedule at the RP2D in TKI naive patients.
Interventions
DRUGFisogatinib (BLU-554)
Sponsors
Blueprint Medicines Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Confirmed diagnosis of HCC by histological examination or by non-invasive criteria according to European Association for the Study of the Liver (EASL) or American Association for the Study of Liver Disease (AASLD) guidelines (Part 1, 2 and 3). * For Part 1 and 2, the patient has unresectable disease and has been previously treated with sorafenib, has declined treatment with sorafenib, or does not have access to sorafenib. * For Part 3, the patient has not received prior treatment with a TKI. * Child-Pugh class A with no clinically apparent ascites * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * For Part 1, willing to provide archived tumor tissue (if available) and willing to undergo pre- and on-treatment tumor biopsy (if considered safe and medically feasible by the treating investigator) * For Part 2 and 3, all patients must have an FGF19 IHC result available. Only FGF19 IHC+ HCC patients will be eligible for Part 3. Key
Exclusion criteria
* Central nervous system metastases * Platelet count \<75,000/mL * Absolute neutrophil count \<1000/mL * Hemoglobin \<8 g/dL * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>5x the upper limit of normal (ULN) * Total bilirubin \>2.5 mg/dL * International normalized ratio (INR) \>2.3 or prothrombin time (PT) \>6 seconds above control * Estimated (Cockroft-Gault formula) or measured creatinine clearance \<40 mL/min
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) on qd and bid schedules | During cycle 1 (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier |
| Recommended Phase 2 dose of fisogatinib (BLU-554) on qd and bid schedules | At the end of every cycle (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier |
| Number of patients with adverse events, serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings | Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levels of FGF19 in blood and tumor samples | Cycle 1 (Day 28) | — |
| Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules | Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study) | Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and end of treatment (EOT) |
| Preliminary evidence of fisogatinib (BLU-554) antineoplastic activity | Screening, Day 1 of every odd numbered cycle starting with Cycle 3, End of treatment (at approximately 24 months or earlier if patient terminates from the study) and every three months post EOT | — |
| Time to maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules | Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study) | Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and EOT |
| Fibroblast growth factor 19 (FGF19) status in tumor tissue | Cycle 2 (Day 56) | — |
Countries
China, France, Germany, Hong Kong, Italy, Singapore, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Outcome results
None listed