E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Unresectable/Metastatic Esophageal Squamous Cell Carcinoma(ESCC)
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E.1.1.1 | Medical condition in easily understood language |
Advanced Unresectable or Metastatic Esophageal Squamous Cell Carcinoma(ESCC) |
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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 | 10055476 |
E.1.2 | Term | Esophageal squamous cell carcinoma |
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 the overall survival (OS) in the Intention-to-Treat (ITT) population following treatment with tislelizumab vs. investigator chosen chemotherapy (ICC) when given as second line treatment in patients with advanced unresectable/metastatic Esophageal Squamous Cell Carcinoma (ESCC) |
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E.2.2 | Secondary objectives of the trial |
Key Secondary Objective:
•To compare the OS in programmed cell death protein ligand-1 (PD-L1) positive population following treatment with tislelizumab versus investigator chosen chemotherapy (ICC)
Other Secondary Objectives:
•The following will be compared between tislelizumab and ICC based on assessment by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria:
o Progression-free survival (PFS)
o Duration of response (DOR)
• To compare patient reported outcomes of health-related quality of life (HRQoL) between the tislelizumab and the chemotherapy treatments
• To compare the safety and tolerability between tislelizumab and the chemotherapy treatments
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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 |
Safety Run-in Substudy Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-PD-1 Monoclonal Antibody BGB A317 in Japanese Patients with Advanced Unresectable/Metastatic Esophageal Squamous Cell Carcinoma
Protocol Identifier: BGB-A317-302 Substudy
Primary Study Objectives:
• To assess the safety and tolerability of BGB-A317 in Japanese patients with advanced unresectable esophageal squamous cell carcinoma (ESCC)
• 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 esophageal squamous cell carcinoma (ESCC)
2. Tumor progression during or after first-line systemic treatment for advanced unresectable / metastatic ESCC
3. At least one measurable/evaluable lesion by RECIST v1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 prior to randomization
5. Adequate End organ function
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E.4 | Principal exclusion criteria |
1. Receipt of 2 or more prior lines of systemic treatments for advanced/metastatic unresectable ESCC
2. History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to randomization
3. Tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula in the study treatment assessed by investigator
4. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage
5. Received prior therapies targeting PD-1 or PD-L1
6. Prior malignancy active within the previous 2 years before randomisation (exceptions include the tumor under investigation in this study, and locally recurring cancers that have undergone curative treatment, such as resected basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast)
7. Active brain or leptomeningeal metastasis.
8. Has active autoimmune disease or history of autoimmune diseases at high risk for relapse
9. Known history of, or any evidence of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis diagnosed based on imaging or clinical findings, or uncontrolled systemic diseases, including diabetes, hypertension, acute lung diseases, etc
10. Known history of Human Immunodeficiency Virus (HIV)
11. Has cardiovascular risk factors
12. Pregnant or breastfeeding woman.
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E.5 End points |
E.5.1 | Primary end point(s) |
• OS in the ITT analysis set- defined as the time from the date of randomization until the date of death due to any cause in all randomized
patients
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final analysis of OS will occur at approximately 3 years |
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E.5.2 | Secondary end point(s) |
Key Secondary Endpoint:
• OS in the PD-L1 positive analysis set - defined as the time from the date of randomization until the date of death due to any cause in the PDL1 positive population
Other Secondary Endpoints:
• ORR in both the ITT analysis set and the PD-L1 positive analysis set - defined as the proportion of patients who had complete response (CR) or partial response (PR) assessed by the Investigators per RECIST v1.1
• PFS in both the ITT analysis set and the PD-L1 positive analysis set - defined as the time from the date of randomization to the date of first
documentation of disease progression assessed by the Investigators per RECIST v1.1 or death, whichever occurs first
• DOR in both the ITT analysis set and the PD-L1 positive analysis set - defined as the time from the first determination of an objective response until the first documentation of progression assessed by the Investigators per RECIST v1.1 or death, whichever comes first
• HRQoL assessment
• The incidence and severity of adverse events
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ORR as assessed by investigator
PFS as assessed by investigator
DOR as assessed by investigator
HRQoL as assessed by European EORTC QLQ-C30 index, the European esophageal cancer specific module OES18, and the EQ-5D-5L.
Incidence and severity of adverse events according to NCI-CTCAE v4.0 |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Assessment of Immunogenicity |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
Japan |
Korea, Republic of |
Taiwan |
Belgium |
France |
Germany |
Italy |
Spain |
United Kingdom |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 2 |