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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
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
Primary outcome measure(s)
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
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. Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval
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. Heart Rate
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
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. Time to reach maximum plasma drug concentration (Tmax) of ERY974
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. Area under the concentration versus time curve (AUC) 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
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. Heart Rate
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. Maximum plasma concentration (Cmax) of ERY974
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. Time to reach maximum plasma drug concentration (Tmax) of ERY974
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. Area under the concentration versus time curve (AUC) of ERY974
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part] — From screening to 6weeks GPC3 and PD-L1 IHC staining
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part] — From screening to 6weeks Immune-related molecule IHC
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part] — From screening to 6weeks Gene expression
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
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, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0
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. Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval
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. Heart Rate
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.