Clinical trial NCT05022927: A Phase I Study of ERY974 in Patients With Hepatocellular Carcinoma
Official title: A PHASE I STUDY OF ERY974 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC HEPATOCELLULAR CARCINOMA
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Hepatocellular Carcinoma (HCC)
Lead sponsor: Chugai Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2021-08-26
Enrollment: 179
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Dose limiting toxicities) [Dose escalation part]
timeFrame: At the end of Cycle 2 (Cycle 1 is 14day, Cycle 2 or later is 21days)
measure: Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab from initiation (Dose limiting toxicities) [Concomitant use part]
timeFrame: At the end of Cycle 1 (each Cycle is 21days)
measure: Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
timeFrame: From screening to 6weeks
measure: Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
timeFrame: From screening to 6weeks
measure: Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
timeFrame: From screening to 6weeks
measure: Anti-tumor activity of ERY974 [Mono dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Secondary outcomes:
measure: Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
timeFrame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks.
measure: Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
timeFrame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks.
measure: Safety of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Biomarker part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 [Mono dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 [Mono dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Pharmacokinetics of ERY974 [Mono dose escalation part]
timeFrame: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
measure: Biomarkers of ERY974 [Mono dose escalation part]
timeFrame: From screening to 6weeks
measure: Biomarkers of ERY974 [Mono dose escalation part]
timeFrame: From screening to 6weeks
measure: Biomarkers of ERY974 [Mono dose escalation part]
timeFrame: From screening to 6weeks
Other outcomes:
Locations:
city: Chiba-shi
country: Japan
facility: Chiba University Hospital
state: Chiba
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: clinical-trials@chugai-pharm.co.jp
name: Sponsor Chugai Pharmaceutical Co. Ltd
role: STUDY_DIRECTOR
References:
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.