Clinical Trials /

A Phase 1 Study of BLU-554 in Patients With Hepatocellular Carcinoma

NCT02508467

Description:

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 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.

Related Conditions:
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title:A Phase 1 Study of BLU-554 in Patients With Hepatocellular Carcinoma
  • Official Title:A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BLU-554 in Patients With Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: BLU-554-1101
  • SECONDARY ID: 2015-001662-26
  • NCT ID: NCT02508467

Trial Conditions

  • Hepatocellular Carcinoma (HCC)

Trial Interventions

DrugSynonymsArms
BLU-554BLU-554

Trial Purpose

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 BLU- 554 administered orally in patients with hepatocellular carcinoma (HCC). The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
BLU-554ExperimentalBLU-554 capsules for oral administration. Each capsule contains 100 mg or 40 mg of active drug substance. BLU-554 will be dosed daily for 28 day cycles. The starting dose will be 140 mg once daily and will increase per protocol
  • BLU-554

Eligibility 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. Patient has unresectable disease and has been previously treated with sorafenib, has declined treatment with sorafenib, or does not have access to sorafenib.

OR

- Confirmed diagnosis of a relapsed or refractory advanced solid tumor other than HCC that has evidence of aberrant FGF19/FGFR4 pathway activity [e.g. tumor or blood/plasma alterations including, but not limited to, 11q13.1 locus (FGF19/CCND1 (cyclin D1)) amplification/copy number gain]

- Child-Pugh class A with no clinically apparent ascites

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- 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)

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

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:During cycle 1 (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier
Safety Issue:Yes
Description:

Secondary Outcome Measures

Measure:Maximum plasma concentration of BLU-554
Time Frame:Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)
Safety Issue:No
Description: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)
Measure:Time to maximum plasma concentration of BLU-554
Time Frame:Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)
Safety Issue:No
Description: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
Measure:Fibroblast growth factor 19 (FGF19) status in tumor tissue
Time Frame:Cycle 2 (Day 56)
Safety Issue:No
Description:
Measure:Levels of FGF19 in blood and tumor samples
Time Frame:Cycle 1 (Day 28)
Safety Issue:No
Description:
Measure:Preliminary evidence of BLU-554 antineoplastic activity
Time Frame:End of treatment (at approximately 24 months or earlier if patient terminates from the study) and every three months post EOT
Safety Issue:No
Description:

Trial 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