Trial Outcomes & Findings for Tislelizumab in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Gastric, or Gastroesophageal Junction Carcinoma (NCT NCT03777657)

Last Updated: 2025-02-14

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

997 participants

Primary outcome timeframe

From randomization up to the primary analysis data cut-off date of 8 October 2021; Median (range) time on follow-up was 11.8 (0.1 - 33.4) months.

Results posted on

2025-02-14

Participant Flow

This study was conducted at 141 study centers in 13 countries across Asia, Europe, and North America. Adults with histologically confirmed, locally advanced unresectable or metastatic gastric or gastrooesophageal junction adenocarcinoma and no previous systemic therapy for advanced disease were recruited.

Participants were randomly assigned to either tislelizumab plus investigator chosen chemotherapy (ICC) or placebo plus ICC. Randomization was stratified according to region (China \[including Taiwan\] vs Japan and South Korea vs Europe/North America), programmed cell death protein ligand-1 (PD-L1) expression (PDL1 tumor area positivity (TAP) score ≥5% or \<5%), peritoneal metastases (yes vs no), and investigator's choice of chemotherapy (capecitabine + oxaliplatin, or 5-fluorouracil + cisplatin).

Participant milestones

Participant milestones
Measure	Tislelizumab + Chemotherapy Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Chemotherapy consisted of 1000 mg/m² capecitabine twice daily on Days 1-14 and 130 mg/m² oxaliplatin on Day 1, or 800 mg/m² 5-fluorouracil (5-FU) on Days 1-5 and 80 mg/m² cisplatin on Day 1 of each 21-day cycle. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Placebo + Chemotherapy Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Chemotherapy consisted of 1000 mg/m² capecitabine twice daily on Days 1-14 and 130 mg/m² oxaliplatin on Day 1, or 800 mg/m² 5-FU on Days 1-5 and 80 mg/m² cisplatin on Day 1 of each 21-day cycle. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Overall Study STARTED	501	496
Overall Study Received Treatment	498	494
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	500	496

Reasons for withdrawal

Reasons for withdrawal
Measure	Tislelizumab + Chemotherapy Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Chemotherapy consisted of 1000 mg/m² capecitabine twice daily on Days 1-14 and 130 mg/m² oxaliplatin on Day 1, or 800 mg/m² 5-fluorouracil (5-FU) on Days 1-5 and 80 mg/m² cisplatin on Day 1 of each 21-day cycle. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Placebo + Chemotherapy Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Chemotherapy consisted of 1000 mg/m² capecitabine twice daily on Days 1-14 and 130 mg/m² oxaliplatin on Day 1, or 800 mg/m² 5-FU on Days 1-5 and 80 mg/m² cisplatin on Day 1 of each 21-day cycle. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Overall Study Death	397	431
Overall Study Study Closed by Sponsor	77	38
Overall Study Withdrawal by Subject	20	17
Overall Study Lost to Follow-up	6	10

Baseline Characteristics

Tislelizumab in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Gastric, or Gastroesophageal Junction Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tislelizumab + Chemotherapy n=501 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Placebo + Chemotherapy n=496 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Total n=997 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	340 Participants n=5 Participants	313 Participants n=7 Participants	653 Participants n=5 Participants
Age, Categorical >=65 years	161 Participants n=5 Participants	183 Participants n=7 Participants	344 Participants n=5 Participants
Age, Continuous	58.8 years STANDARD_DEVIATION 11.07 • n=5 Participants	59.7 years STANDARD_DEVIATION 11.20 • n=7 Participants	59.3 years STANDARD_DEVIATION 11.14 • n=5 Participants
Sex: Female, Male Female	155 Participants n=5 Participants	150 Participants n=7 Participants	305 Participants n=5 Participants
Sex: Female, Male Male	346 Participants n=5 Participants	346 Participants n=7 Participants	692 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	492 Participants n=5 Participants	474 Participants n=7 Participants	966 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	16 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized Asian	376 Participants n=5 Participants	372 Participants n=7 Participants	748 Participants n=5 Participants
Race/Ethnicity, Customized White	116 Participants n=5 Participants	107 Participants n=7 Participants	223 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	8 Participants n=5 Participants	16 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Geographic Region China (including Taiwan)	259 Participants n=5 Participants	257 Participants n=7 Participants	516 Participants n=5 Participants
Geographic Region Japan and South Korea	117 Participants n=5 Participants	115 Participants n=7 Participants	232 Participants n=5 Participants
Geographic Region North America/Europe	125 Participants n=5 Participants	124 Participants n=7 Participants	249 Participants n=5 Participants
Primary Tumor Location Stomach	405 Participants n=5 Participants	395 Participants n=7 Participants	800 Participants n=5 Participants
Primary Tumor Location Gastro-oesophageal junction	96 Participants n=5 Participants	100 Participants n=7 Participants	196 Participants n=5 Participants
Primary Tumor Location Other*	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
PD-L1 Expression < 5%	227 Participants n=5 Participants	224 Participants n=7 Participants	451 Participants n=5 Participants
PD-L1 Expression ≥ 5%	274 Participants n=5 Participants	272 Participants n=7 Participants	546 Participants n=5 Participants
Presence of Peritoneal Metastasis Yes	220 Participants n=5 Participants	214 Participants n=7 Participants	434 Participants n=5 Participants
Presence of Peritoneal Metastasis No	281 Participants n=5 Participants	282 Participants n=7 Participants	563 Participants n=5 Participants
Investigator Chosen Chemotherapy Oxaliplatin + Capecitabine	466 Participants n=5 Participants	465 Participants n=7 Participants	931 Participants n=5 Participants
Investigator Chosen Chemotherapy Cisplatin + 5-Fluorouracil	35 Participants n=5 Participants	31 Participants n=7 Participants	66 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization up to the primary analysis data cut-off date of 8 October 2021; Median (range) time on follow-up was 11.8 (0.1 - 33.4) months.

Population: The PD-L1-Positive Analysis Set included all randomized participants whose tumors were PD-L1 positive (defined as PD-L1 TAP score ≥ 5%)

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

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=272 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=274 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Overall Survival in PD-L1 Positive Participants	12.6 months Interval 12.0 to 14.4	17.2 months Interval 13.9 to 21.3

PRIMARY outcome

Timeframe: From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.

Population: The Intent-to-Treat (ITT) Analysis Set included all randomized participants.

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

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=496 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=501 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Overall Survival in the Intent-to-Treat (ITT) Analysis Set	12.9 months Interval 12.1 to 14.1	15.0 months Interval 13.6 to 16.5

SECONDARY outcome

Timeframe: From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.

Population: PD-L1 Positive Analysis Set

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

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=272 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=274 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Progression-free Survival (PFS) in PD-L1 Positive Participants	5.9 months Interval 5.6 to 7.0	7.2 months Interval 5.8 to 8.4

SECONDARY outcome

Timeframe: Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.

Population: PD-L1 Positive Analysis Set

ORR is defined as the percentage of participants whose best overall response is complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors v1.1 assessed by the investigator. Investigators conducted assessments of radiological tumor response by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST version 1.1 about every six weeks during the first 48 weeks of the study and every nine weeks thereafter. CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=272 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=274 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Overall Response Rate (ORR) in PD-L1 Positive Participants	42.6 percentage of participants Interval 36.7 to 48.8	51.5 percentage of participants Interval 45.4 to 57.5

SECONDARY outcome

Timeframe: From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.

Population: Intent-to-Treat Analysis Set

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=496 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=501 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Progression-free Survival (PFS) in the ITT Analysis Set	6.2 months Interval 5.6 to 6.9	6.9 months Interval 5.7 to 7.2

SECONDARY outcome

Population: Intent-to-Treat (ITT) Analysis Set

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=496 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=501 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Overall Response Rate (ORR) in the ITT Analysis Set	40.5 percentage of participants Interval 36.2 to 45.0	47.3 percentage of participants Interval 42.9 to 51.8

SECONDARY outcome

Population: Participants in the PD-L1 Positive Analysis Set with an objective response

DOR is defined as the time from the first determination of an objective response assessed by the investigator per RECIST v1.1, until the first documentation of progression or death, whichever occurred first. Progressive disease (PD): At least a 20% increase in the size of target lesions, taking as reference the smallest size on study, with an absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or any new lesions.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=116 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=141 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Duration of Response (DOR) in PD-L1 Positive Participants	6.9 months Interval 5.7 to 8.5	10.0 months Interval 8.2 to 16.8

SECONDARY outcome

Population: Participants in the ITT Analysis Set with an objective response

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=201 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=237 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Duration of Response in the ITT Analysis Set	7.2 months Interval 6.0 to 8.5	8.6 months Interval 7.9 to 11.1

SECONDARY outcome

Timeframe: Baseline and Cycles 4 and 6

Population: Participants in the ITT Analysis Set who completed the EORTC QLQ-C30 at baseline; participants with available data at baseline and the relevant postbaseline visit are included in the analysis at each time point.

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.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=467 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=465 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) and Physical Functioning Scores Global Health Status/QOL: Cycle 4	-0.45 score on a scale Interval -2.04 to 1.13	1.35 score on a scale Interval -0.24 to 2.94
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) and Physical Functioning Scores Global Health Status/QOL: Cycle 6	-1.58 score on a scale Interval -3.24 to 0.07	0.93 score on a scale Interval -0.71 to 2.57
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) and Physical Functioning Scores Physical Functioning: Cycle 4	-3.92 score on a scale Interval -5.21 to -2.62	-2.47 score on a scale Interval -3.77 to -1.18
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) and Physical Functioning Scores Physical Functioning: Cycle 6	-5.22 score on a scale Interval -6.69 to -3.75	-2.76 score on a scale Interval -4.22 to -1.3

SECONDARY outcome

Timeframe: Baseline and Cycles 4 and 6

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.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=467 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=465 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Change From Baseline in EORTC QLQ-C30 Fatigue Score Cycle 4	3.07 score on a scale Interval 1.23 to 4.91	1.75 score on a scale Interval -0.09 to 3.6
Change From Baseline in EORTC QLQ-C30 Fatigue Score Cycle 6	4.73 score on a scale Interval 2.68 to 6.77	1.71 score on a scale Interval -0.32 to 3.75

SECONDARY outcome

Timeframe: Baseline and Cycles 4 and 6

Population: Participants in the ITT Analysis Set who completed the EORTC QLQ-STO22 at baseline; participants with available data at baseline and the relevant postbaseline visit are included in the analysis at each time point.

EORTC-QLQ-STO22 is a 22-item questionnaire developed to assess QoL of gastric cancer participants. It consists of 5 multi-item subscales: Dysphagia/odynophagia (4 items), Pain/discomfort (3 items), Dietary restrictions (5 items), Upper gastro-intestinal (GI) symptoms (3 items), Specific emotional problems (3 items) and 4 single items. Each question is answered on a scale from 0 (Not at all) to 4 (Very Much), where lower scores indicate fewer symptoms/better QoL. Raw scores were transformed to a scale from 0 to 100, where lower scores indicate better QoL. The QLQ-STO22 Index score is the mean of the 6 domain scores and 4 single items.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=467 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=465 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) Index Score: Cycle 4	-0.61 units on a scale Interval -1.66 to 0.45	-1.71 units on a scale Interval -2.77 to -0.66
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) Index Score: Cycle 6	-0.22 units on a scale Interval -1.34 to 0.89	-1.84 units on a scale Interval -2.95 to -0.74
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) Dysphagia/Odynophagia Scale: Cycle 4	-1.27 units on a scale Interval -2.48 to -0.06	-2.78 units on a scale Interval -3.99 to -1.57
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) Dysphagia/Odynophagia Scale: Cycle 6	-2.01 units on a scale Interval -3.17 to -0.86	-2.79 units on a scale Interval -3.93 to -1.64
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) Pain/Discomfort Scale: Cycle 4	-4.64 units on a scale Interval -6.16 to -3.13	-6.88 units on a scale Interval -8.39 to -5.36
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) Pain/Discomfort Scale: Cycle 6	-4.09 units on a scale Interval -5.69 to -2.49	-5.97 units on a scale Interval -7.56 to -4.38
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) Dietary Restrictions Scale: Cycle 4	0.61 units on a scale Interval -0.82 to 2.05	-0.31 units on a scale Interval -1.75 to 1.12
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) Dietary Restrictions Scale: Cycle 6	1.08 units on a scale Interval -0.48 to 2.63	-0.25 units on a scale Interval -1.79 to 1.3
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) Upper Gastro-Intestinal Symptoms: Cycle 4	-1.54 units on a scale Interval -2.8 to -0.28	-3.14 units on a scale Interval -4.4 to -1.87
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) Upper Gastro-Intestinal Symptoms: Cycle 6	-1.49 units on a scale Interval -2.84 to -0.14	-3.24 units on a scale Interval -4.58 to -1.9

SECONDARY outcome

Timeframe: Baseline and Cycles 4 and 6

Population: Participants in the ITT Analysis Set who completed the EQ-5D-5L at baseline; participants with available data at baseline and the relevant postbaseline visit are included in the analysis at each time point.

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.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=467 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=465 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Change From Baseline in European Quality of Life 5-Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS) Cycle 6	-0.8 score on a scale Standard Deviation 15.17	3.0 score on a scale Standard Deviation 16.38
Change From Baseline in European Quality of Life 5-Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS) Cycle 4	0.8 score on a scale Standard Deviation 14.91	2.9 score on a scale Standard Deviation 15.62

SECONDARY outcome

Timeframe: From first dose of study drug to 30 days after last dose or the initiation of a new anticancer therapy, whichever occurred first, up to the end of study; maximum treatment duration was 59.3 months in Tislelizumab and 56.8 months in the Placebo group.

Population: The Safety Analysis Set included all participants who received ≥ 1 dose of study drug

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.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=494 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=498 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any TEAE	486 Participants	495 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any SAE	179 Participants	211 Participants

SECONDARY outcome

Population: PD-L1 Positive Analysis Set

Disease Control Rate is defined as the percentage of participants who had confirmed CR, PR, or stable disease (SD) assessed by the investigator and the investigator per RECIST v1.1. Investigators conducted assessments of radiological tumor response by CT or MRI per RECIST version 1.1 about every six weeks during the first 48 weeks of the study and every nine weeks thereafter. CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. SD: Neither sufficient shrinkage in size of lesions to qualify for PR nor sufficient increase to qualify for PD, and no new lesions.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=272 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=274 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Disease Control Rate in PD-L1 Positive Participants	83.1 percentage of participants Interval 78.1 to 87.3	88.3 percentage of participants Interval 83.9 to 91.9

SECONDARY outcome

Population: ITT Analysis Set

Disease Control Rate is defined as the percentage of participants who had confirmed CR, PR, or stable disease (SD) assessed by the investigator per RECIST v1.1. Investigators conducted assessments of radiological tumor response by CT or MRI per RECIST version 1.1 about every six weeks during the first 48 weeks of the study and every nine weeks thereafter. CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. SD: Neither sufficient shrinkage in size of lesions to qualify for PR nor sufficient increase to qualify for PD, and no new lesions.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=496 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=501 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Disease Control Rate in the ITT Analysis Set	83.3 percentage of participants Interval 79.7 to 86.4	89.8 percentage of participants Interval 86.8 to 92.3

SECONDARY outcome

Population: PD-L1 Positive Analysis Set

Clinical benefit rate is defined as the percentage of participants who achieved a confirmed complete response, partial response, or durable stable disease assessed by the Investigator per RECIST v1.1. CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. Durable SD: Stable disease for ≥ 24 weeks.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=272 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=274 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Clinical Benefit Rate (CBR) in PD-L1 Positive Participants	59.2 percentage of participants Interval 53.1 to 65.1	65.0 percentage of participants Interval 59.0 to 70.6

SECONDARY outcome

Population: ITT Analysis Set

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=496 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=501 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Clinical Benefit Rate (CBR) in the ITT Analysis Set	58.9 percentage of participants Interval 54.4 to 63.2	63.1 percentage of participants Interval 58.7 to 67.3

SECONDARY outcome

Timeframe: From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.

Population: Participants in the PD-L1 Positive Analysis Set with an objective response

Time to response is defined as the time from randomization to the first determination of an objective response per RECIST version 1.1 as assessed by the investigator.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=116 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=141 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Time to Response (TTR) in PD-L1 Positive Participants	1.4 months Interval 1.0 to 17.5	1.4 months Interval 0.9 to 11.3

SECONDARY outcome

Timeframe: From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.

Population: Participants in the ITT Analysis Set with an objective response

Time to response is defined as the time from randomization to the first determination of an objective response per RECIST version 1.1 as assessed by the investigator.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=201 Participants Participants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.	Tislelizumab + Chemotherapy n=237 Participants Participants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Time to Response (TTR) in the ITT Analysis Set	1.4 months Interval 1.0 to 17.5	1.4 months Interval 0.9 to 13.4

Adverse Events

Tislelizumab + Chemotherapy

Serious events: 211 serious events

Other events: 489 other events

Deaths: 397 deaths

Placebo + Chemotherapy

Serious events: 179 serious events

Other events: 485 other events

Deaths: 431 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

BeiGene

Phone: 877-828-5568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information \& may request a further delay to protect its IP rights.
Publication restrictions are in place

Restriction type: OTHER