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Completed

NCT Number: NCT03777657

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

This study was designed to compare the efficacy and safety of tislelizumab plus chemotherapy versus placebo plus chemotherapy as the first treatment (first-line) for adults diagnosed with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

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Key information

Conditions

Gastric, or Gastroesophageal Junction Adenocarcinoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Locally advanced unresectable or metastatic gastric cancer (GC) or gastroesophageal junction (GEJ) carcinoma and have histologically confirmed adenocarcinoma
  • No previous systemic therapy for locally advanced unresectable or metastatic gastric/GEJ cancer. NOTE: Participants may have received prior neoadjuvant or adjuvant therapy as long as it was completed and have no recurrence or disease progression for at least 6 months.
  • Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1 within 7 days prior to randomization
  • Adequate organ function ≤ 7 days prior to randomization

Key Exclusion Criteria:

  • Has squamous cell or undifferentiated or other histological type GC
  • Active leptomeningeal disease or uncontrolled brain metastasis
  • Diagnosed with gastric or GEJ adenocarcinoma with positive HER2
  • Prior therapy with an anti-programmed cell death protein-1 (PD-1), anti-programmed cell death protein ligand-1 (PD-L1), anti-programmed cell death protein ligand-2 (PD-L2), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment and study plan

Tislelizumab

Drug

200 mg intravenously (IV) on Day 1 of each 21-day cycle

Other names: BGB-A317, TEVIMBRA®

Placebo

Drug

Placebo to match tislelizumab IV on Day 1 of each 21-day cycle

Cisplatin

Drug

80 mg/m² IV on Day 1 of each 21-day cycle

Oxaliplatin

Drug

130 mg/m² IV on Day 1 of each 21-day cycle

Capecitabine

Drug

1000 mg/m² orally twice daily (BD) Days 1 through 14 (14 days total) of each 21-day cycle

5-fluorouracil

Drug

800 mg/m²/day IV using continuous infusion on Days 1 to 5 of each 21-day cycle

Primary outcomes

  1. Overall Survival in PD-L1 Positive Participants

    Time frame: 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.

    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.

  2. Overall Survival in the Intent-to-Treat (ITT) Analysis Set

    Time frame: 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.

    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.

Secondary outcomes

  1. Progression-free Survival (PFS) in PD-L1 Positive Participants

    Time frame: 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.

    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.

  2. Overall Response Rate (ORR) in PD-L1 Positive Participants

    Time frame: 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.

    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.

  3. Progression-free Survival (PFS) in the ITT Analysis Set

    Time frame: 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.

    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.

  4. Overall Response Rate (ORR) in the ITT Analysis Set

    Time frame: 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.

    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.

  5. Duration of Response (DOR) in PD-L1 Positive Participants

    Time frame: 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.

    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.

  6. Duration of Response in the ITT Analysis Set

    Time frame: 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.

    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.

  7. 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

    Time frame: 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. Higher scores in GHS and functional scales indicate better quality of life.

  8. Change From Baseline in EORTC QLQ-C30 Fatigue Score

    Time frame: 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.

  9. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22)

    Time frame: Baseline and Cycles 4 and 6

    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.

  10. Change From Baseline in European Quality of Life 5-Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS)

    Time frame: Baseline and Cycles 4 and 6

    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.

  11. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Time frame: 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.

    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.

  12. Disease Control Rate in PD-L1 Positive Participants

    Time frame: 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.

    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.

  13. Disease Control Rate in the ITT Analysis Set

    Time frame: 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.

    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.

  14. Clinical Benefit Rate (CBR) in PD-L1 Positive Participants

    Time frame: 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.

    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.

  15. Clinical Benefit Rate (CBR) in the ITT Analysis Set

    Time frame: 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.

    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.

  16. Time to Response (TTR) in PD-L1 Positive Participants

    Time frame: 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.

    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.

  17. Time to Response (TTR) in the ITT Analysis Set

    Time frame: 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.

    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.

Sponsors and collaborators

Lead sponsor

BeiGene

Industry

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Clinical Study Comparing the Efficacy and Safety of Tislelizumab (BGB-A317) Plus Platinum and Fluoropyrimidine Versus Placebo Plus Platinum and Fluoropyrimidine as First-Line Treatment in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Important dates

Study start
2018
Primary completion
2023
Study completion
2024
First posted
Dec 17, 2018
Registry last updated
Feb 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.