A Phase I Study of ERY974 in Patients With Hepatocellular Carcinoma

Hepatocellular Carcinoma (HCC) Clinical Trial

Official title:

A PHASE I STUDY OF ERY974 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC HEPATOCELLULAR CARCINOMA

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05022927
• Other study ID #: ERY103JG
• Status: Recruiting
• Phase: Phase 1
• Start date: June 1, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: Chugai Pharmaceutical
• Contact: Clinical trials information
• Phone: Only use Email
• Email: clinical-trials[@]chugai-pharm.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 179
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma (HCC)

Intervention

Drug:
• ERY974
ERY974 vial
• Tocilicumab
Tocilizumab vial
• Atezolizumab
Atezolizumab vial
• Bevacizumab
Bevacizumab vial

Locations

Country	Name	City	State
Japan	Chiba University Hospital	Chiba-shi	Chiba
Japan	National Cancer Center Hospital	Chuo Ku	Tokyo
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Kindai University Hospital	Osakasayama	Osaka
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chi Mei Medical Center	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Chugai Pharmaceutical

Countries where clinical trial is conducted

Japan,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Dose limiting toxicities) [Dose escalation part]	Incidence and nature of DLTs	At the end of Cycle 2 (Cycle 1 is 14day, Cycle 2 or later is 21days)
Primary	Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]	Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]	Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]	Heart Rate	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]	Maximum plasma concentration (Cmax) of ERY974 Maximum plasma concentration (Cmax) of ERY974 Maximum plasma concentration (Cmax) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]	Time to reach maximum plasma drug concentration (Tmax) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]	Area under the concentration versus time curve (AUC) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]	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)	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab from initiation (Dose limiting toxicities) [Concomitant use part]	Incidence and nature of DLTs	At the end of Cycle 1 (each Cycle is 21days)
Primary	Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]	Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]	Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]	Heart Rate	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]	Maximum plasma concentration (Cmax) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]	Time to reach maximum plasma drug concentration (Tmax) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]	Area under the concentration versus time curve (AUC) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]	GPC3 and PD-L1 IHC staining	From screening to 6weeks
Primary	Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]	Immune-related molecule IHC	From screening to 6weeks
Primary	Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]	Gene expression	From screening to 6weeks
Primary	Anti-tumor activity of ERY974 [Mono dose escalation part]	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)	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]	Incidence and nature of DLTs	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]	Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]	Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Primary	Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]	Heart Rate	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]	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)	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks.
Secondary	Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]	Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]	Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]	Heart Rate	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]	Maximum plasma concentration (Cmax) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]	Time to reach maximum plasma drug concentration (Tmax) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]	Area under the concentration versus time curve (AUC) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]	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)	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks.
Secondary	Safety of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]	Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Biomarker part]	Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.	Heart Rate	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]	Maximum plasma concentration (Cmax) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]	Time to reach maximum plasma drug concentration (Tmax) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]	Time to reach maximum plasma drug concentration (AUC) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Pharmacokinetics of ERY974 [Mono dose escalation part]	Maximum plasma concentration (Cmax) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Pharmacokinetics of ERY974 [Mono dose escalation part]	Time to reach maximum plasma drug concentration (Tmax) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Pharmacokinetics of ERY974 [Mono dose escalation part]	Area under the concentration versus time curve (AUC) of ERY974	From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary	Biomarkers of ERY974 [Mono dose escalation part]	GPC3 IHC staining	From screening to 6weeks
Secondary	Biomarkers of ERY974 [Mono dose escalation part]	Immune-related molecule IHC	From screening to 6weeks
Secondary	Biomarkers of ERY974 [Mono dose escalation part]	Gene expression	From screening to 6weeks