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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Expansion part | Experimental | 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 | Experimental | Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD. |
|
| Biomarker part | Experimental | 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 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ERY974 | Drug | ERY974 vial |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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] |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sponsor Chugai Pharmaceutical Co. Ltd | clinical-trials@chugai-pharm.co.jp | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chiba University Hospital | Chiba | Chiba | 260-8677 | Japan | ||
| National Cancer Center Hospital East |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35853994 | Derived | 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. |
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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).
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C000717791 | bispecific antibody ERY974 |
| C000594389 | atezolizumab |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Experimental |
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. |
|
| Tocilicumab | Drug | Tocilizumab vial |
|
| Atezolizumab | Drug | Atezolizumab vial |
|
| Bevacizumab | Drug | Bevacizumab vial |
|
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. |
| 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. |
| 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 | 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] | 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] | 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 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] | 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] | 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] | 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] | 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 | 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] | 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 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 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] | 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 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] | 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] | GPC3 IHC staining | From screening to 6weeks |
| Biomarkers of ERY974 [Mono dose escalation part] | Immune-related molecule IHC | From screening to 6weeks |
| Biomarkers of ERY974 [Mono dose escalation part] | Gene expression | From screening to 6weeks |
| Kashiwa |
| Chiba |
| 277-8577 |
| Japan |
| Kanagawa Cancer Center | Yokohama | Kanagawa | 241-8515 | Japan |
| Kindai University Hospital | Sayama | Osaka | 589-8511 | Japan |
| National Cancer Center Hospital | Chuo Ku | Tokyo | 104-0045 | Japan |
| Kaohsiung Chang Gung Memorial Hospital | Kaohsiung City | 83301 | Taiwan |
| Taichung Veterans General Hospital | Taichung | 40705 | Taiwan |
| National Cheng Kung University Hospital | Tainan | 70142 | Taiwan |
| Chi Mei Medical Center | Tainan | 71004 | Taiwan |
| National Taiwan University Hospital | Taipei | 100 | Taiwan |
| Linkou Chang Gung Memorial Hospital | Taoyuan | 33305 | Taiwan |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |