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.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

179

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Jun 2021

Longer than P75 for phase_1

Geographic Reach

2 countries

11 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.6 years study duration

Study Start

First participant enrolled

June 1, 2021

Completed

27 days until next milestone

First Submitted

Initial submission to the registry

June 28, 2021

Completed

2 months until next milestone

First Posted

Study publicly available on registry

August 26, 2021

Completed

4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2025

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2025

Completed

Last Updated

September 5, 2024

Status Verified

September 1, 2024

Enrollment Period

4.6 years

First QC Date

June 28, 2021

Last Update Submit

September 2, 2024

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (23)

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)
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.
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.
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.
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.
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.
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.
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.
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)
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.
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.
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.
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.
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.
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.
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
GPC3 and PD-L1 IHC staining
From screening to 6weeks
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Immune-related molecule IHC
From screening to 6weeks
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
Gene expression
From screening to 6weeks
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.
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.
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.
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.
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 Outcomes (20)

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.
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.
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.
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.
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.
+15 more secondary outcomes

Study Arms (5)

Dose escalation part

EXPERIMENTAL

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.