A Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Participants With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Carcinoma

Investigator-Assessed PFS

PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause (whichever occurred first), as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).

Time frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 19 months)

IRF-Assessed Confirmed Objective Response Rate (ORR)

IRF- assessed confirmed ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) as determined by an IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR

Time frame: From randomization up to approximately 19 months

Investigator-Assessed Confirmed ORR

Investigator-assessed confirmed ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR

Time frame: From randomization up to approximately 19 months

IRF-Assessed Duration of Objective Response (DOR)

DOR was defined as the time from the first occurrence of a documented objective response (OR) to progressive disease (PD) or death from any cause (whichever occurred first) as determined by an IRF according to RECIST v1.1. OR=CR+PR. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm.

Time frame: From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 19 months)

Investigator-Assessed DOR

DOR was defined as the time from the first occurrence of a documented objective response (OR) to progressive disease (PD) or death from any cause (whichever occurred first) as determined by the investigator according to RECIST v1.1. OR=CR+PR. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm.

Time frame: From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 19 months)

Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning as Measured by EORTC QLQ-C30

Clinically meaningful changes in physical functioning as measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30). EORTC QLQ-C30 is a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) within the previous week. Physical functioning was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning. Participants were considered "Worsened" if their baseline score decreased by \>/=10 points.

Time frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 27 months)

TTCD in Participant-Reported Role Functioning as Measured by EORTC QLQ-C30

Clinically meaningful changes in role functioning as measured by the EORTC QLQ-C30. EORTC QLQ-C30 is a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) within the previous week. Functioning items were scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning. Participants were considered "Worsened" if their baseline score decreased by \>/=10 points.

Time frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 27 months)

TTCD in Participant-Reported Global Health Status (GHS)/Quality of Life (QoL) as Measured by EORTC QLQ-C30

Clinically meaningful changes in GHS/QoL as measured by the EORTC QLQ-C30. EORTC QLQ-C30 is a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) within the previous week. GHS and QoL items were scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores were linearly transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better GHS/QoL. Participants were considered "Worsened" if their baseline score decreased by \>/=10 points.

Time frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 27 months)

TTCD in Participant-Reported Dysphagia as Measured by EORTC Quality of Life-Esophageal Cancer, Module 18 Questionnaire (EORTC QLQ-OES18)

Clinically meaningful changes in dysphagia as measured by the EORTC QLQ-OES18. EORTC QLQ-OES18 is a modular supplement to the EORTC QLQ-C30 questionnaire for use in participants with esophageal cancer. EORTC QLQ-OES18 consisted of 4 multiple-item scale (dysphagia, eating, reflux, and pain) and 6 single items (trouble swallowing saliva, choked when swallowing, dry mouth, trouble with taste, trouble with coughing, and trouble talking) with a recall period of the previous week. Each symptom item was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to a range of 0 to 100, with higher transformed scores (i.e. closer to 100) reflecting worse symptoms. Participants were considered "Worsened" if their baseline score increased by \>/=10 points.

Time frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months)

Percentage of Participants With Adverse Events (AEs)

An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Time frame: Up to approximately 35 months

Minimum Serum Concentration (Cmin) of Tiragolumab

As indicated in the row titles of the table Cmin of Cycle 1 was measured predose at Cycle (C) 2 Day (D) 1. Cmin of Cycle 2 was measured predose at C3D1, etc.

Time frame: Predose at on Day 1 of Cycles (cycle=21 days) 2, 3, 4, 8, 12, 16

Maximum Serum Concentration (Cmax) of Tiragolumab

Time frame: Cycle 1 (cycle=21 days), Day 1: 30 minutes postdose

Cmin of Atezolizumab

As indicated in the row titles of the table Cmin of Cycle 1 was measured predose at Cycle (C) 2 Day (D) 1. Cmin of Cycle 2 was measured predose at C3D1, etc.

Time frame: Predose at on Day 1 of Cycles (cycle=21 days) 2, 3, 4, 8, 12, 16

Cmax of Atezolizumab

Time frame: Cycle 1 (cycle=21 days), Day 1: 30 minutes postdose

Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab

Participants were considered to be anti-drug antibody (ADA) positive if they were ADA negative or had missing data at Baseline but developed an ADA response following study drug exposure (i.e., treatment-induced ADA positive), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (i.e., treatment-enhanced ADA positive); these ADA positive responses are summarized together (induced + enhanced) in the 'treatment-emergent ADA positive' category.

Time frame: Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 35 months)

Number of Participants Positive for ADAs to Atezolizumab

Participants were considered to be anti-drug antibody (ADA) positive if they were ADA negative or had missing data at Baseline but developed an ADA response following study drug exposure (i.e., treatment-induced ADA positive), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (i.e., treatment-enhanced ADA positive); these ADA positive responses are summarized together (induced + enhanced) in the 'treatment-emergent ADA positive' category.

Time frame: Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 35 months)