search
Back to results

A Phase I Study of ERY974 in Patients With Hepatocellular Carcinoma

Primary Purpose

Hepatocellular Carcinoma (HCC)

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ERY974
Tocilicumab
Atezolizumab
Bevacizumab
Sponsored by
Chugai Pharmaceutical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma (HCC)

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Aged ≥20 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

Sites / Locations

  • Chiba University HospitalRecruiting
  • National Cancer Center Hospital EastRecruiting
  • Kanagawa Cancer CenterRecruiting
  • Kindai University HospitalRecruiting
  • National Cancer Center HospitalRecruiting
  • Chi Mei Medical CenterRecruiting
  • National Taiwan University HospitalRecruiting
  • Linkou Chang Gung Memorial HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose escalation part

Expansion part

Concomitant use part

Biomarker part

Arm Description

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.

Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect.

Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD.

Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers.

Outcomes

Primary Outcome Measures

Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Dose limiting toxicities) [Dose escalation part]
Incidence and nature of DLTs
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
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
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
Heart Rate
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
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
Time to reach maximum plasma drug concentration (Tmax) of ERY974
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
Area under the concentration versus time curve (AUC) of ERY974
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)
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab from initiation (Dose limiting toxicities) [Concomitant use part]
Incidence and nature of DLTs
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
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
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Heart Rate
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Maximum plasma concentration (Cmax) of ERY974
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Time to reach maximum plasma drug concentration (Tmax) of ERY974
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Area under the concentration versus time curve (AUC) of ERY974
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
GPC3 and PD-L1 IHC staining
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Immune-related molecule IHC
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Gene expression

Secondary Outcome Measures

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)
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
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
Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Heart Rate
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Maximum plasma concentration (Cmax) of ERY974
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Time to reach maximum plasma drug concentration (Tmax) of ERY974
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Area under the concentration versus time curve (AUC) of ERY974
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)
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
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.
Heart Rate
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Maximum plasma concentration (Cmax) of ERY974
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Time to reach maximum plasma drug concentration (Tmax) of ERY974
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Area under the concentration versus time curve (AUC) of ERY974

Full Information

First Posted
June 28, 2021
Last Updated
July 7, 2023
Sponsor
Chugai Pharmaceutical
search

1. Study Identification

Unique Protocol Identification Number
NCT05022927
Brief Title
A Phase I Study of ERY974 in Patients With Hepatocellular Carcinoma
Official Title
A Phase I Study of ERY974 in Combination With ATEZOLIZUMAB and BEVACIZUMAB in Patients With Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2021 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chugai Pharmaceutical

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma (HCC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
158 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose escalation part
Arm Type
Experimental
Arm Description
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.
Arm Title
Expansion part
Arm Type
Experimental
Arm Description
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect.
Arm Title
Concomitant use part
Arm Type
Experimental
Arm Description
Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD.
Arm Title
Biomarker part
Arm Type
Experimental
Arm Description
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers.
Intervention Type
Drug
Intervention Name(s)
ERY974
Intervention Description
ERY974 vial
Intervention Type
Drug
Intervention Name(s)
Tocilicumab
Intervention Description
Tocilizumab vial
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Intervention Description
Atezolizumab vial
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Bevacizumab vial
Primary Outcome Measure Information:
Title
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Dose limiting toxicities) [Dose escalation part]
Description
Incidence and nature of DLTs
Time Frame
At the end of Cycle 2 (Cycle 1 is 14day, Cycle 2 or later is 21days)
Title
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
Description
Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
Description
Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
Description
Heart Rate
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
Description
Maximum plasma concentration (Cmax) of ERY974 Maximum plasma concentration (Cmax) of ERY974 Maximum plasma concentration (Cmax) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
Description
Time to reach maximum plasma drug concentration (Tmax) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
Description
Area under the concentration versus time curve (AUC) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Description
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)
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab from initiation (Dose limiting toxicities) [Concomitant use part]
Description
Incidence and nature of DLTs
Time Frame
At the end of Cycle 1 (each Cycle is 21days)
Title
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Description
Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Description
Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Description
Heart Rate
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Description
Maximum plasma concentration (Cmax) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Description
Time to reach maximum plasma drug concentration (Tmax) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Description
Area under the concentration versus time curve (AUC) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Description
GPC3 and PD-L1 IHC staining
Time Frame
From screening to 6weeks
Title
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Description
Immune-related molecule IHC
Time Frame
From screening to 6weeks
Title
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Description
Gene expression
Time Frame
From screening to 6weeks
Secondary Outcome Measure Information:
Title
Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
Description
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)
Time Frame
From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks.
Title
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Description
Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Description
Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Description
Heart Rate
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Description
Maximum plasma concentration (Cmax) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Description
Time to reach maximum plasma drug concentration (Tmax) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
Description
Area under the concentration versus time curve (AUC) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
Description
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)
Time Frame
From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks.
Title
Safety of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
Description
Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Biomarker part]
Description
Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Description
Heart Rate
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Description
Maximum plasma concentration (Cmax) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Description
Time to reach maximum plasma drug concentration (Tmax) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Title
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Description
Area under the concentration versus time curve (AUC) of ERY974
Time Frame
From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical trials information
Phone
Only use Email
Email
clinical-trials@chugai-pharm.co.jp
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sponsor Chugai Pharmaceutical Co. Ltd
Organizational Affiliation
clinical-trials@chugai-pharm.co.jp
Official's Role
Study Director
Facility Information:
Facility Name
Chiba University Hospital
City
Chiba-shi
State/Province
Chiba
ZIP/Postal Code
260-8677
Country
Japan
Individual Site Status
Recruiting
Facility Name
National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Individual Site Status
Recruiting
Facility Name
Kanagawa Cancer Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
241-8515
Country
Japan
Individual Site Status
Recruiting
Facility Name
Kindai University Hospital
City
Osakasayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
Individual Site Status
Recruiting
Facility Name
National Cancer Center Hospital
City
Chuo Ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Individual Site Status
Recruiting
Facility Name
Chi Mei Medical Center
City
Tainan
ZIP/Postal Code
71004
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Linkou Chang Gung Memorial Hospital
City
Taoyuan
ZIP/Postal Code
33305
Country
Taiwan
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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).
Citations:
PubMed Identifier
35853994
Citation
Komatsu SI, Kayukawa Y, Miyazaki Y, Kaneko A, Ikegami H, Ishiguro T, Nakamura M, Frings W, Ono N, Sakata K, Fujii T, Kishishita S, Kitazawa T, Endo M, Sano Y. Determination of starting dose of the T cell-redirecting bispecific antibody ERY974 targeting glypican-3 in first-in-human clinical trial. Sci Rep. 2022 Jul 19;12(1):12312. doi: 10.1038/s41598-022-16564-x.
Results Reference
derived

Learn more about this trial

A Phase I Study of ERY974 in Patients With Hepatocellular Carcinoma

We'll reach out to this number within 24 hrs