A Study of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma

Overall survival is defined as the time from the date of randomization until the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method.

Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority.

Progression-free survival is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.

Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or unequivocal progression of existing nontarget lesions, or the appearance of 1 or more new lesions.

Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.

ORR is defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) assessed by the investigator per RECIST v1.1. Tumor assessments included computed tomography (CT) scans or magnetic resonance imaging (MRI), with preference for CT, of the neck, chest, and abdomen.

CR: Disappearance of all target and nontarget lesions with no new lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm.

PR: Disappearance of all target lesions with persistence of 1 or more nontarget lesion(s), no new lesions, and/or maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis (data cutoff date of 28 February 2022).

OS is defined as the time from the date of randomization until the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method.

Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.

DOR is defined as the time from the first determination of an objective response until the first documentation of progression assessed by the investigator per RECIST v1.1 or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method.

Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.

The EORTC-QLQ-OES18 is the specific esophageal symptoms module of the QLQ-C30. QLQ-OES18 is comprised of 18 questions grouped into 4 multi-item subscales: Dysphagia (3 items), Eating (4 items), Reflux (2 items), and Pain (3 items) and 6 single item subscales (trouble swallowing saliva, choking, dry mouth, taste, coughing, and talking). Participants indicate the extent to which they have experienced symptoms on a scale from 1 (Not at all) to 4 (Very much). Scores are calculated as the average of the items that contribute to the scale, then transformed to a scale from 0 to 100. The OES18 index score is calculated as the average of the 4 multi-item subscales and 6 single-item subscales. Higher scores indicate a higher level of symptomatology or problems.

The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and 2 global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed to a 0 to 100 scale via linear transformation. Higher scores in GHS and functional scales indicate better quality of life.

The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and 2 global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed to a 0 to 100 scale via linear transformation. The fatigue symptom scale includes 3 items and ranges from 0 to 100, where higher scores indicate a higher level of symptoms.

The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drugs, whether related to study drugs or not.

An SAE is any untoward medical occurrence that, at any dose met any of the following criteria:

• Resulted in death
• Was life-threatening
• Required hospitalization or prolongation of existing hospitalization
• Resulted in disability/incapacity
• Was a congenital anomaly/birth defect
• Was considered a significant medical AE by the Investigator based on medical judgement.