E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable Hepatocellular Carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Unresectable Hepatocellular Carcinoma is a specific type of Liver cancer that is unable to be removed by surgery. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019828 |
E.1.2 | Term | Hepatocellular carcinoma non-resectable |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare OS between Tislelizumab and sorafenib as first-line treatment in patients with unresectable HCC |
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E.2.2 | Secondary objectives of the trial |
•To compare ORR assessed by Blinded Independent Review Committee (BIRC) according to Response Evaluation Criteria in Solid Tumors [RECIST]) Version (v)1.1 between Tislelizumab and sorafenib
• To compare progression-free survival (PFS) assessed by BIRC according to RECIST v1.1 between Tislelizumab and sorafenib
• To compare DOR assessed by BIRC according to RECIST v1.1 between Tislelizumab and sorafenib
• To compare time to progression (TTP) between Tislelizumab and sorafenib
• To compare health-related quality of life (HRQoL) between Tislelizumab and sorafenib
• To compare tumor assessment outcomes (ie, ORR, PFS, DOR, TTP) assessed by Investigator according to RECIST v1.1 between Tislelizumab and sorafenib
• To compare disease control rate (DCR) and clinical benefit rate (CBR), assessed by BIRC and Investigator according to RECIST v1.1, between Tislelizumab and sorafenib
• To compare safety and tolerability of Tislelizumab versus sorafenib |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: SAFETY RUN-IN SUBSTUDY INVESTIGATING SAFETY, TOLERABILITY, PHARMACOKINETICS AND PRELIMINARY ANTITUMOR ACTIVITY OF ANTI-PD-1 MONOCLONAL ANTIBODY BGB-A317 IN JAPANESE PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA
Protocol Identifier: BGB-A317-301 Substudy
Primary Study Objectives:
• To assess the safety and tolerability of BGB-A317 in Japanese patients with hepatocellular carcinoma (HCC)
• To confirm the pivotal Phase 3 dose of BGB-A317 in Japanese patients
• To characterize the pharmacokinetics of BGB-A317 in Japanese patients
Secondary Study Objectives:
• To assess the preliminary antitumor activity of BGB-A317
• To assess host immunogenicity to BGB-A317 |
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E.3 | Principal inclusion criteria |
1. Histologically confirmed diagnosis of HCC
2. Barcelona Clinic Liver Cancer (BCLC) Stage B or C disease not amenable to or progressing after loco-regional therapy and not amenable to a curative treatment approach
3. No prior systemic therapy for HCC (with the exception of HCC patients enrolled in the safety run-in substudy [Japan only])
4. Measurable disease
5. Child-Pugh score A
6. Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1
7. Adequate organ function |
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E.4 | Principal exclusion criteria |
1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
2. Tumor thrombus involving main trunk of portal vein or inferior vena cava
3. Loco-regional therapy to the liver within 28 days before randomization
4. Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization
5. Bleeding or thrombotic disorder or any prescribed anticoagulant requiring therapeutic international normalized ratio monitoring (eg, warfarin or similar agents) at Screening, or within 6 months before randomization/enrollment
6. Presence at Screening of active immune deficiency or autoimmune disease and/or prior history of any immune deficiency or autoimmune disease that may relapse
7. Patient with any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before randomization
8. History of interstitial lung disease or non-infectious pneumonitis, unless induced by radiation therapy
9. QT interval corrected for heart rate (QTc) (corrected by Fridericia’s method) > 450 msec at Screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Overall Survival (OS) – defined as the time from the date of randomization to the date of death due to any cause |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
OS assessed by Blinded Independent Review Committee (BIRC) |
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E.5.2 | Secondary end point(s) |
• Overall Response Rate (ORR) as assessed by BIRC – defined as the proportion of patients with a documented CR or PR per RECIST v1.1
• Progression-free survival (PFS)– defined as the time from the date of randomization to the date of the first objectively documented tumor progression, assessed by BIRC per RECIST v1.1, or death, whichever occurs first
• Duration of response (DOR) – defined as the time from the first determination of an objective response, assessed by BIRC per RECIST v1.1, until the first documentation of progression or death, whichever occurs first
• Time to progression (TTP) – defined as the time from the date of randomization to the date of the first objectively documented tumor progression, assessed by BIRC per RECIST v1.1
• Health-related quality of life (HRQoL)
• Tumor assessment (ie, ORR, PFS, DOR and TTP), assessed by Investigator per RECIST v1.1
• Disease control rate (DCR) – defined as the proportion of patients whose best overall response (BOR) is CR, PR, or SD, assessed by BIRC and Investigator per RECIST v1.1
• Clinical benefit rate (CBR) – defined as the proportion of patients who have CR, PR, or SD of ≥ 24 weeks in duration, assessed by BIRC and Investigator per RECIST v1.1
• Safety assessment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• ORR by BIRC
• PFS by BIRC
• DOR by BIRC
• TTP by BIRC
• HRQoL
• Tumor assessments (ORR, PFS, DOR, and TTP) assessed by Investigator per RECIST v1.1
• DCR by BIRC and Investigator
• CBR by BIRC and Investigator
• Safety assessment (eg, new adverse events [AEs], AEs present at baseline that worsen in severity during the study, and clinical laboratory abnormalities) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
China |
European Union |
Japan |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |