E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
PD-L1 vCPS ≥ 10% Unresectable, Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Esophageal Squamous Cell Carcinoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
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 the objective response rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), of tislelizumab plus BGB-A1217 with tislelizumab plus placebo as second-line treatment in patients with programmed cell death ligand-1 (PD-L1) visually-estimated Combined Positive Score (vCPS) ≥ 10% unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in the Intentto-Treat (ITT) Analysis Set.
• To compare the overall survival (OS) of tislelizumab plus BGB-A1217 with tislelizumab plus placebo as second-line treatment in patients with PD-L1 vCPS ≥ 10% ESCC in the ITT Analysis Set. |
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E.2.2 | Secondary objectives of the trial |
• To compare the following endpoints between tislelizumab plus BGBA1217 and tislelizumab plus placebo based on tumor assessments per RECIST v1.1: 1-Progression-free survival (PFS) assessed by both the Independent Review Committee (IRC) and the investigator. 2-Duration of response (DOR), disease control rate (DCR), and clinical benefit rate (CBR) assessed by both the IRC and the investigator. 3-ORR assessed by the IRC.
• To compare the safety and tolerability between tislelizumab plus BGBA1217 and tislelizumab plus placebo.
• To compare the health-related quality of life (HRQoL) via cancerspecific patient-reported outcomes (PROs) between tislelizumab plus BGB-A1217 and tislelizumab plus placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed diagnosis of ESCC.
2. Have PD during or after first-line of systemic treatment for unresectable, locally advanced, recurrent or metastatic ESCC.
3. Have measurable disease as assessed by RECIST v1.1.
4. Have confirmed PD-L1 vCPS ≥ 10% in tumor tissues tested by the central lab.
5. ECOG PS score of 0 or 1. |
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E.4 | Principal exclusion criteria |
1. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.
2. Patients with evidence of fistula (either esophageal/bronchial or esophageal/aorta).
3. Evidence of complete esophageal obstruction not amenable to treatment.
4. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks after intervention).
5. Has received any chemotherapy, immunotherapy (eg, interleukin, interferon, thymosin, etc) or any investigational therapies within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug. Or has received palliative radiation treatment or other local regional therapies within 14 days before the first dose of study drug. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• ORR, defined as the proportion of patients in the ITT Analysis Set who have complete response (CR) or partial response (PR) as assessed by the investigator per RECIST v1.1.
• OS, defined as the time from the date of randomization until the date of death due to any cause in patients in the ITT Analysis Set. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint ORR will be tested at a 1-sided alpha of 0.025. If the null hypothesis for ORR in the ITT Analysis Set is rejected, OS will be tested hierarchically in the ITT Analysis Set. The inferential test for OS will be stopped at the non-significant final analysis of ORR in the ITT Analysis Set. The familywise type I error will be strongly controlled at one-sided level 0.025. |
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E.5.2 | Secondary end point(s) |
• ORR, defined as above and assessed by the IRC per RECIST v1.1 in the ITT Analysis Set.
• PFS, defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) assessed by both the IRC and investigator per RECIST v1.1 or death, whichever occurs first in the ITT Analysis Set.
• DOR, defined as the time from the first determination of an objective response until the first documentation of PD as assessed by both the IRC and the investigator per RECIST v1.1, or death, whichever comes first in the ITT Analysis Set.
• DCR, defined as the proportion of patients in the ITT Analysis Set who have CR, PR, and stable disease assessed by both the IRC and the investigator per RECIST v1.1.
• CBR, defined as the proportion of patients who achieve CR, PR and durable stable disease (stable disease ≥24 weeks).
• HRQoL, measured by the Global Health Status (GHS)/QoL and Physical Function scales of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and scores of Dysphagia, Eating, Reflux and Pain of EORTC Quality of Life Oesophageal Cancer Questionnaires 18 (QLQ-OES18).
• Adverse events (AEs) and serious adverse events (SAEs) as characterized by type, frequency, severity (as graded by the National Cancer Institute-Common Terminology Criteria for Adverse Events [NCICTCAE] version 5.0 [v5.0]), timing, seriousness, and relationship to study drugs, physical examinations, electrocardiograms (ECGs), and laboratory assessments. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ORR assessed by the IRC per RECIST v1.1 in the ITT Analysis Set will be analyzed similarly to the corresponding analysis of ORR assessed by the investigator.
PFS based on assessment by the IRC and the investigator per RECIST v1.1 will be analyzed in the ITT Analysis Set. The PFS censoring rule will follow the United States (US) Food and Drug Administration (FDA) Guidance for Industry.
DOR will be analyzed among the responders in the ITT Analysis Set using methods similar to that described for PFS, based on assessment by the IRC and the investigator.
DCR and CBR assessed by the IRC and investigator per RECIST v1.1 will be summarized similarly as ORR in the ITT Analysis Set and the EAS. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 |
Korea, Republic of |
Russian Federation |
Taiwan |
Ukraine |
Belgium |
France |
Spain |
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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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Last information being collected from the last patient. The last information is defined as the information of death, withdraw consent, completed all study assessments or lost follow-up. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |