A Phase I Study of ERY974 in Patients With Hepatocellular Carcinoma

September 2, 2024 updated by: Chugai Pharmaceutical

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

179

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Chiba
      • Chiba-shi, Chiba, Japan, 260-8677
        • Chiba University Hospital
      • Kashiwa, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 241-8515
        • Kanagawa Cancer Center
    • Osaka
      • Osakasayama, Osaka, Japan, 589-8511
        • Kindai University Hospital
    • Tokyo
      • Chuo Ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
  • Taiwan
      • Kaohsiung, Taiwan, 83301
        • Kaohsiung Chang Gung Memorial Hospital
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Tainan, Taiwan, 71004
        • Chi Mei Medical Center
      • Tainan, Taiwan, 70142
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
      • Taoyuan, Taiwan, 33305
        • Linkou Chang Gung Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose escalation part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to determine the MTD by evaluating DLTs of in patients with locally advanced or metastatic HCC.
Drug: ERY974
ERY974 vial
Drug: Tocilicumab
Tocilizumab vial
Drug: Atezolizumab
Atezolizumab vial
Drug: Bevacizumab
Bevacizumab vial
Experimental: Expansion part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect.
Drug: ERY974
ERY974 vial
Drug: Tocilicumab
Tocilizumab vial
Drug: Atezolizumab
Atezolizumab vial
Drug: Bevacizumab
Bevacizumab vial
Experimental: Concomitant use part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD.
Drug: ERY974
ERY974 vial
Drug: Tocilicumab
Tocilizumab vial
Drug: Atezolizumab
Atezolizumab vial
Drug: Bevacizumab
Bevacizumab vial
Experimental: Biomarker part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers.
Drug: ERY974
ERY974 vial
Drug: Tocilicumab
Tocilizumab vial
Drug: Atezolizumab
Atezolizumab vial
Drug: Bevacizumab
Bevacizumab vial
Experimental: Mono dose escalation part
Patients will receive ERY974 as a single agent and to determine the MTD by evaluating DLTs of in patients with locally advanced or metastatic HCC.
Drug: ERY974
ERY974 vial
Drug: Tocilicumab
Tocilizumab vial
Drug: Atezolizumab
Atezolizumab vial
Drug: Bevacizumab
Bevacizumab vial

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Dose limiting toxicities) [Dose escalation part]
Time Frame: At the end of Cycle 2 (Cycle 1 is 14day, Cycle 2 or later is 21days)
Incidence and nature of DLTs
At the end of Cycle 2 (Cycle 1 is 14day, Cycle 2 or later is 21days)
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
Time Frame: 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.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Time Frame: 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)
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab from initiation (Dose limiting toxicities) [Concomitant use part]
Time Frame: At the end of Cycle 1 (each Cycle is 21days)
Incidence and nature of DLTs
At the end of Cycle 1 (each Cycle is 21days)
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Time Frame: 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.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Time Frame: From screening to 6weeks
GPC3 and PD-L1 IHC staining
From screening to 6weeks
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Time Frame: From screening to 6weeks
Immune-related molecule IHC
From screening to 6weeks
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Time Frame: From screening to 6weeks
Gene expression
From screening to 6weeks
Anti-tumor activity of ERY974 [Mono dose escalation part]
Time Frame: 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)
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]
Time Frame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Incidence and nature of DLTs
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]
Time Frame: 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
Time Frame: 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)
From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks.
Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Time Frame: 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.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Time Frame: 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)
From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks.
Safety of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Biomarker part]
Time Frame: 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
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.
Time Frame: 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.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Time Frame: 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 (AUC) of ERY974
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 [Mono dose escalation part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 [Mono dose escalation part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Pharmacokinetics of ERY974 [Mono dose escalation part]
Time Frame: 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
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Biomarkers of ERY974 [Mono dose escalation part]
Time Frame: From screening to 6weeks
GPC3 IHC staining
From screening to 6weeks
Biomarkers of ERY974 [Mono dose escalation part]
Time Frame: From screening to 6weeks
Immune-related molecule IHC
From screening to 6weeks
Biomarkers of ERY974 [Mono dose escalation part]
Time Frame: From screening to 6weeks
Gene expression
From screening to 6weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chugai Pharmaceutical

Investigators

  • Study Director: Sponsor Chugai Pharmaceutical Co. Ltd, clinical-trials@chugai-pharm.co.jp

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2021

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

June 28, 2021

First Submitted That Met QC Criteria

August 24, 2021

First Posted (Actual)

August 26, 2021

Study Record Updates

Last Update Posted (Estimated)

September 5, 2024

Last Update Submitted That Met QC Criteria

September 2, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ERY103JG

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform. For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html).

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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