E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable Hepatocellular Carcinoma |
Carcinome hépatocellulaire non résécable |
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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 | 20.0 |
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 BGB-A317 and sorafenib as first-line treatment in patients with unresectable HCC |
Comparer la survie globale (SG) entre le BGB-A317 et le sorafénib comme traitement de première ligne chez des patients atteints d’un carcinome hépatocellulaire (CHC) non résécable |
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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 BGB-A317 and sorafenib
• To compare progression-free survival (PFS) assessed by BIRC according to RECIST v1.1 between BGB-A317 and sorafenib
• To compare DOR assessed by BIRC according to RECIST v1.1 between BGB-A317 and sorafenib
• To compare time to progression (TTP) between BGB-A317 and sorafenib
• To compare health-related quality of life (HRQoL) between BGB-A317 and sorafenib
• To compare tumor assessment outcomes (ie, ORR, PFS, DOR, TTP) assessed by Investigator according to RECIST v1.1 between BGB-A317 and sorafenib
• To compare disease control rate (DCR) and clinical benefit rate (CBR), assessed by BIRC and Investigator according to RECIST v1.1, between BGB-A317 and sorafenib
• To compare safety and tolerability of BGB-A317 versus sorafenib |
•Comparer le taux de réponse objective (TRO) évalué par un comité d’examen indépendant en aveugle (BIRC) conformément aux critères d’évaluation de la réponse dans les tumeurs solides (RECIST) Version 1.1 entre le BGB-A317 et le sorafénib.
•Comparer la survie sans progression (SSP) évaluée par le BIRC entre le BGB-A317 et le sorafénib
•Comparer la durée de réponse (DDR) évaluée par le BIRC entre le BGB-A317 et le sorafénib
•Comparer le délai avant progression (DAP) entre le BGB-A317 et le sorafénib
•Comparer la qualité de vie liée à la santé (QdVLS)
•Comparer les résultats relatifs à l’évaluation de la tumeur (c.-à-d. TRO, SSP, DDR, DAP) évalués par l’investigateur selon les critères RECIST v1.1 entre le BGB-A317 et le sorafénib
•Comparer le taux de contrôle de la maladie (TCM) et le taux de bénéfice clinique (TBC), évalués par le BIRC et l’investigateur selon les critères RECIST v1.1
•Comparer la sécurité d’emploi et la tolérance du BGB-A317 comparativement au sorafénib |
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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 |
1.Présenter un diagnostic de CHC confirmé par histologie
2.Etre atteint(e) d’une maladie au stade C (BCLC) ou d’une maladie au stade B selon la BCLC qui ne se prête par à un traitement loco-régional ou a progressé après un tel traitement, et ne se prête pas à une approche de traitement curatif
3.Ne pas avoir reçu de traitement systémique antérieur pour le CHC
4.Présenter une lésion mesurable
5.Présenter une classification Child-Pugh A
6.Présenter un score PS ECOG ≤ 1
7.Présenter une fonction organique adéquate
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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 |
1.Présente un CHC fibrolamellaire, un CHC sarcomatoïde, une forme mixte associant un cholangiocarcinome à un CHC
2.Présente un thrombus tumoral impliquant le tronc principal de la veine porte ou la veine cave inférieure
3.A reçu dans les 28 jours précédant la randomisation un traitement loco-régional pour le foie
4.Présente à la sélection, ou a présenté dans les 6 mois précédant la randomisation, toute preuve clinique d’hypertension portale accompagnée de varices Å“sophagiennes ou gastriques hémorragiques
5.Présente à la sélection, ou a présenté dans les 6 mois précédant la randomisation, un saignement ou un trouble thrombotique ou a pris un anticoagulant prescrit nécessitant une surveillance thérapeutique du rapport normalisé international (INR) (par ex. warfarine ou agents similaires)
6.Présente à la sélection un déficit immunitaire actif ou une maladie auto-immune et/ou a des antécédents de déficit immunitaire ou de maladie auto-immune qui pourrait rechuter
7.Présente une maladie qui a nécessité un traitement systémique par corticoïdes (> 10 mg par jour de prednisone ou équivalent) ou par d’autres médicaments immunosuppresseurs dans les 14 jours précédant la randomisation
8.Présente des antécédents de maladie pulmonaire interstitielle ou de pneumopathie inflammatoire non infectieuse, sauf si elle est induite par radiothérapie
9.17.Présente des ECG à la sélection montrant un intervalle QT corrigé (QTc) pour la fréquence cardiaque (corrigé par la méthode de Fridericia) > 450 msec |
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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 |
•Survie globale (SG) - définie par le temps passé entre la date de randomisation et la date du décès pour quelque raison que ce soit |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
OS assessed by Blinded Independent Review Committee (BIRC) |
Survie globale (SG) définie par le 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 | 14 |
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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LVLS |
Dernière visite du dernier patient |
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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 | 8 |
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 |