A Phase I Study of ERY974 in Patients With Hepatocellular Carcinoma
- Conditions
- Hepatocellular Carcinoma (HCC)
- Interventions
- Registration Number
- NCT05022927
- Lead Sponsor
- Chugai Pharmaceutical
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 179
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Concomitant use part ERY974 Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD. Dose escalation part ERY974 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. Dose escalation part Tocilicumab 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. Expansion part Bevacizumab Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect. Expansion part ERY974 Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect. Expansion part Tocilicumab Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect. Concomitant use part Tocilicumab Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD. Biomarker part Tocilicumab Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers. Biomarker part ERY974 Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers. Mono dose escalation part Tocilicumab 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. Mono dose escalation part ERY974 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. Expansion part Atezolizumab Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect. Dose escalation part Atezolizumab 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. Dose escalation part Bevacizumab 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. Concomitant use part Atezolizumab Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD. Concomitant use part Bevacizumab Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD. Biomarker part Atezolizumab Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers. Biomarker part Bevacizumab Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers. Mono dose escalation part Atezolizumab 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. Mono dose escalation part Bevacizumab 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.
- Primary Outcome Measures
Name Time Method 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
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
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 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
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
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
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)
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 Gene expression
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
- Secondary Outcome Measures
Name Time Method 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. 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] 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
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. Heart Rate
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
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
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. Area under the concentration versus time curve (AUC) of ERY974
Biomarkers of ERY974 [Mono dose escalation part] From screening to 6weeks Gene expression
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. Time to reach maximum plasma drug concentration (AUC) of ERY974
Trial Locations
- Locations (11)
Chiba University Hospital
🇯🇵Chiba-shi, Chiba, Japan
Kanagawa Cancer Center
🇯🇵Yokohama, Kanagawa, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Kindai University Hospital
🇯🇵Osakasayama, Osaka, Japan
National Cancer Center Hospital
🇯🇵Chuo Ku, Tokyo, Japan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Chi Mei Medical Center
🇨🇳Tainan, Taiwan
Linkou Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan