Hepatocellular Carcinoma (HCC)
Conditions
Brief summary
This is a multicenter, open-label, dose-escalation study designed to determine the maximum tolerated dose (MTD) by evaluating dose-limiting toxicities (DLTs) and to evaluate the safety, tolerability, pharmacokinetics, anti-tumor effect, and biomarkers of ERY974 in combination with atezolizumab and bevacizumab following premedication with tocilizumab in patients with locally advanced or metastatic HCC.
Interventions
DRUGERY974
ERY974 vial
DRUGTocilicumab
Tocilizumab vial
DRUGAtezolizumab
Atezolizumab vial
DRUGBevacizumab
Bevacizumab vial
Sponsors
Chugai Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged ≥18 years at time of informed consent * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 * HCC that has been histologically confirmed
Exclusion criteria
* Previous or concomitant autoimmune disease * Uncontrolled diabetes mellitus and hypertension * Concurrent New York Heart Association (NYHA) Class ≥II congestive heart failure, myocardial infarction, arrhythmia, or unstable angina, or a history thereof within 6 months before enrollment. * Concurrent symptomatic cerebrovascular disorder (e.g., subarachnoid hemorrhage, cerebral infarction, or transient ischemic attack), or a history thereof within 6 months before enrollment. * Symptomatic, untreated, or actively progressing CNS metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part] | From screening to 6weeks | GPC3 and PD-L1 IHC staining |
| Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Dose limiting toxicities) [Dose escalation part] | At the end of Cycle 2 (Cycle 1 is 14day, Cycle 2 or later is 21days) | Incidence and nature of DLTs |
| Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0 |
| Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Maximum plasma concentration (Cmax) of ERY974 Maximum plasma concentration (Cmax) of ERY974 Maximum plasma concentration (Cmax) of ERY974 |
| Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Expansion part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Objective Response Rate (ORR) is defined as proportion of patients who had a confirmed complete response (CR) or partial response (PR), as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) |
| Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab from initiation (Dose limiting toxicities) [Concomitant use part] | At the end of Cycle 1 (each Cycle is 21days) | Incidence and nature of DLTs |
| Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0 |
| Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval |
| Anti-tumor activity of ERY974 [Mono dose escalation part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Objective Response Rate (ORR) is defined as proportion of patients who had a confirmed complete response (CR) or partial response (PR), as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) |
| Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Incidence and nature of DLTs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Biomarker part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval |
| Biomarkers of ERY974 [Mono dose escalation part] | From screening to 6weeks | GPC3 IHC staining |
| From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Heart Rate |
| Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part] | From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks. | Objective Response Rate (ORR) is defined as proportion of patients who had a confirmed complete response (CR) or partial response (PR), as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) |
| Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0 |
| Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval |
| Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Maximum plasma concentration (Cmax) of ERY974 |
| Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part] | From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks. | Objective Response Rate (ORR) is defined as proportion of patients who had a confirmed complete response (CR) or partial response (PR), as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) |
| Safety of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0 |
| Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Maximum plasma concentration (Cmax) of ERY974 |
| Pharmacokinetics of ERY974 [Mono dose escalation part] | From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks. | Maximum plasma concentration (Cmax) of ERY974 |
Countries
Japan, Taiwan
Outcome results
None listed