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NCT04732494: AdvanTIG-203

Anti-PD-1 Monoclonal Antibody Tislelizumab (BGB-A317) Combined With or Without Anti-TIGIT Monoclonal Antibody Ociperlimab (BGB-A1217) in Participants With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

Completed Phase 2 Results posted Last updated 31 January 2025
What this trial tests

Phase 2 trial testing Tislelizumab in Esophageal Squamous Cell Carcinoma in 125 participants. Completed in 26 December 2023.

Timeline
31 March 2021
Primary endpoint
1 February 2023
26 December 2023

Quick facts

Lead sponsorBeiGene
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment125
Start date31 March 2021
Primary completion1 February 2023
Estimated completion26 December 2023
Sites86 locations across France, Taiwan, South Korea, Thailand, China, Spain

Drugs / interventions tested

Conditions studied

Sponsor

BeiGene — full company profile →

Who can join

18 and older, any sex, with Esophageal Squamous Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Assessed by the Investigator Primary · Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.

Objective response rate is defined as the percentage of participants who had a best overall response of confirmed complete response (CR) or partial response (PR) assessed by the Investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Response evaluations were performed using computed tomography or magnetic resonance imaging (MRI) approximately every 6 weeks for the first 54 weeks and then every 12 weeks thereafter. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) \< 10 mm, and no new lesions.

GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab30.619.6 – 43.7
Arm B: Tislelizumab Plus Placebo20.611.5 – 32.7
Overall Survival Secondary · From randomization to the end of the study, median (range) time on follow-up was 10.0 (0.5 - 29.9) months in Arm A and 7.8 (0.4 - 29.3) months in Arm B.

Overall survival (OS) is defined as the time from the date of randomization until the date of death due to any cause. Median overall survival was estimated using the Kaplan-Meier method. For participants who were still alive at the end of the trial, OS was censored at the last known alive date or the date of data cutoff, whichever was earlier.

GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab10.27.9 – 19.5
Arm B: Tislelizumab Plus Placebo9.36.4 – 14.8
Objective Response Rate Assessed by the Independent Review Committee Secondary · Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.

Objective response rate is defined as the percentage of participants who had a best overall response of confirmed complete response (CR) or partial response (PR) assessed by the Independent Review Committee (IRC) according to RECIST v1.1. Response evaluations were performed using computed tomography or MRI approximately every 6 weeks for the first 54 weeks and then every 12 weeks thereafter. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) \< 10 mm, and no new lesions. PR: At least a 30% decrease in the size of target lesion

GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab32.320.9 – 45.3
Arm B: Tislelizumab Plus Placebo25.415.3 – 37.9
Progression-free Survival (PFS) Assessed by the Independent Review Committee Secondary · From randomization up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.

Progression-free survival is defined as the time from the date of randomization to the date of first documentation of progressive disease assessed by the Independent Review Committee per RECIST v1.1, or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): At least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions, or the appearance of any new lesions.

GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab3.62.7 – 5.1
Arm B: Tislelizumab Plus Placebo2.81.9 – 6.9
Progression-free Survival (PFS) Assessed by the Investigator Secondary · From randomization to the end of the study, median (range) time on follow-up was 10.0 (0.5 - 29.9) months in Arm A and 7.8 (0.4 - 29.3) months in Arm B.

Progression-free survival is defined as the time from the date of randomization to the date of first documentation of progressive disease assessed by the Investigator per RECIST v1.1, or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): At least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions, or the appearance of any new lesions.

GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab3.41.8 – 5.1
Arm B: Tislelizumab Plus Placebo3.41.9 – 4.1
Duration Of Response (DOR) Assessed by the Independent Review Committee Secondary · From randomization up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.

Duration of response is defined as the time from the first determination of an objective response (CR or PR) until the first documentation of progressive disease as assessed by the Independent Review Committee per RECIST v1.1, or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method.

GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab14.67.2 – NA
Arm B: Tislelizumab Plus PlaceboNA4.2 – NA
Duration Of Response (DOR) Assessed by the Investigator Secondary · From randomization to the end of the study, median (range) time on follow-up was 10.0 (0.5 - 29.9) months in Arm A and 7.8 (0.4 - 29.3) months in Arm B.

Duration of response is defined as the time from the first determination of an objective response (CR or PR) until the first documentation of progressive disease as assessed by the Investigator per RECIST v1.1, or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method.

GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab11.35.7 – NA
Arm B: Tislelizumab Plus PlaceboNA4.1 – NA
Disease Control Rate Assessed by the IRC And the Investigator Secondary · Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.

Disease Control Rate is defined as the percentage of participants who had confirmed CR, PR, or stable disease (SD) assessed by the IRC and the investigator per RECIST v1.1. Response evaluations were performed using computed tomography or MRI approximately every 6 weeks for the first 54 weeks and then every 12 weeks thereafter. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) \< 10 mm, and no new lesions. PR: At least a 30% decrease in the size of target lesions, with no progression of non-target lesions and no new lesions, or

Investigator assessment
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab61.348.1 – 73.4
Arm B: Tislelizumab Plus Placebo58.745.6 – 71.0
Independent Review Committee
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab64.551.3 – 76.3
Arm B: Tislelizumab Plus Placebo58.745.6 – 71.0
Clinical Benefit Rate Assessed by the IRC and the Investigator Secondary · Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.

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 IRC and the Investigator per RECIST v1.1. Response evaluations were performed using computed tomography or MRI approximately every 6 weeks for the first 54 weeks and then every 12 weeks thereafter. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) \< 10 mm, and no new lesions. PR: At least a 30% decrease in the size of target lesions, with no progression of n

Investigator Assessment
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab33.922.3 – 47.0
Arm B: Tislelizumab Plus Placebo30.219.2 – 43.0
Independent Review Committee
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab32.320.9 – 45.3
Arm B: Tislelizumab Plus Placebo27.016.6 – 39.7
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 Secondary · Baseline, Cycle 5 Day 1 and Cycle 7 Day 1 (each cycle was 3 weeks)

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

Global Health Status/QOL: Cycle 5
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab1.7-5.6 – 8.9
Arm B: Tislelizumab Plus Placebo-0.1-7.5 – 7.4
Global Health Status/QOL: Cycle 7
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab0.3-5.6 – 6.1
Arm B: Tislelizumab Plus Placebo-2.8-8.8 – 3.2
Physical Functioning: Cycle 5
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab-0.5-4.3 – 3.3
Arm B: Tislelizumab Plus Placebo1.2-2.8 – 5.2
Physical Functioning: Cycle 7
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab-4.4-11.2 – 2.5
Arm B: Tislelizumab Plus Placebo-3.9-11.0 – 3.3
Change From Baseline in EORTC Quality of Life Oesophageal Cancer Questionnaires 18 (QLQ-OES18) Dysphagia, Eating, Reflux and Pain Scales Secondary · Baseline, Cycle 5 Day 1 and Cycle 7 Day 1 (each cycle was 3 weeks)

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 (saliva swallowing, 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 and transformed to a scale from 0 to 100; higher scores indicate a higher level of symptomatology or problems.

Dysphagia: Cycle 5
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab-5.9-14.2 – 2.4
Arm B: Tislelizumab Plus Placebo4.1-4.7 – 12.8
Dysphagia: Cycle 7
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab-3.5-15.4 – 8.5
Arm B: Tislelizumab Plus Placebo7.3-5.2 – 19.8
Eating: Cycle 5
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab-1.6-6.6 – 3.3
Arm B: Tislelizumab Plus Placebo-1.3-6.6 – 4.1
Eating: Cycle 7
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab-2.8-9.1 – 3.6
Arm B: Tislelizumab Plus Placebo6.6-0.2 – 13.4
Reflux: Cycle 5
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab1.9-4.6 – 8.3
Arm B: Tislelizumab Plus Placebo-0.4-7.1 – 6.4
Reflux: Cycle 7
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab2.7-4.8 – 10.1
Arm B: Tislelizumab Plus Placebo4.0-3.8 – 11.8
Pain: Cycle 5
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab0.1-5.5 – 5.6
Arm B: Tislelizumab Plus Placebo-0.7-6.5 – 5.1
Pain: Cycle 7
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab-2.1-7.1 – 3.0
Arm B: Tislelizumab Plus Placebo3.3-2.0 – 8.5
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Secondary · From first dose of study drug until 30 days after last dose; median duration of treatment was 3.45 months in Tislelizumab + Ociperlimab arm and 2.79 months in the Tislelizumab + Placebo arm.

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: * 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. AEs were considered "rela

Any TEAE
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab58
Arm B: Tislelizumab Plus Placebo60
TEAE ≥ Grade 3
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab28
Arm B: Tislelizumab Plus Placebo28
Serious AEs
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab27
Arm B: Tislelizumab Plus Placebo28
Related SAEs
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab13
Arm B: Tislelizumab Plus Placebo13
TEAEs Leading to Treatment Discontinuation
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab9
Arm B: Tislelizumab Plus Placebo10
TEAEs Leading to Death (Excluding Due to Disease Under Study)
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab4
Arm B: Tislelizumab Plus Placebo4
Any Immune-Mediated AE
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab31
Arm B: Tislelizumab Plus Placebo21
Immune-Mediated AE ≥ Grade 3
GroupValue95% CI
Arm A: Tislelizumab Plus Ociperlimab8
Arm B: Tislelizumab Plus Placebo3

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality is reported from randomization through the end of study; up to 30 months. AEs are reported from first dose of study drug until 30 days after last dose; median duration of treatment was 3.45 months in Tislelizumab + Ociperlimab arm and 2.79 months in the Tislelizumab + Placebo arm.. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A: Tislelizumab Plus Ociperlimab
Serious: 27/62 (44%)
Deaths: 39/62
Arm B: Tislelizumab Plus Placebo
Serious: 28/63 (44%)
Deaths: 36/63

Serious adverse events (56 terms)

ReactionSystemArm A: Tislelizumab Plus O…Arm B: Tislelizumab Plus P…
PneumoniaInfections and infestations
PneumonitisRespiratory, thoracic and mediastinal disorders
Oesophageal obstructionGastrointestinal disorders
DeathGeneral disorders
MalaiseGeneral disorders
PyrexiaGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
MalnutritionMetabolism and nutrition disorders
Tumour haemorrhageNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AnaemiaBlood and lymphatic system disorders
Angina unstableCardiac disorders
Arteriosclerosis coronary arteryCardiac disorders
Immune-mediated myocarditisCardiac disorders
MyocarditisCardiac disorders
Pericardial effusionCardiac disorders
TachycardiaCardiac disorders
Adrenal insufficiencyEndocrine disorders
HypophysitisEndocrine disorders
Secondary adrenocortical insufficiencyEndocrine disorders
DysphagiaGastrointestinal disorders
Impaired gastric emptyingGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
Oesophageal fistulaGastrointestinal disorders
Oesophageal stenosisGastrointestinal disorders
Oesophageal ulcerGastrointestinal disorders
Other adverse events (86 terms — click to expand)

ReactionSystemArm A: Tislelizumab Plus O…Arm B: Tislelizumab Plus P…
AnaemiaBlood and lymphatic system disorders
HypothyroidismEndocrine disorders
ConstipationGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Decreased appetiteMetabolism and nutrition disorders
Weight decreasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
FatigueGeneral disorders
Aspartate aminotransferase increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
RashSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
COVID-19Infections and infestations
Upper respiratory tract infectionInfections and infestations
Lymphocyte count decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Blood creatine phosphokinase increasedInvestigations
InsomniaPsychiatric disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
DysphagiaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
PneumoniaInfections and infestations
Neutrophil count decreasedInvestigations
White blood cell count decreasedInvestigations
HypercalcaemiaMetabolism and nutrition disorders
HypochloraemiaMetabolism and nutrition disorders
Cancer painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DizzinessNervous system disorders
HeadacheNervous system disorders
Productive coughRespiratory, thoracic and mediastinal disorders
HyperthyroidismEndocrine disorders

Most-reported serious reactions: Pneumonia, Pneumonitis, Oesophageal obstruction, Death, Malaise, Pyrexia, Hyperglycaemia, Malnutrition.

Data from ClinicalTrials.gov NCT04732494 adverse events section.

Sponsor's own description

A study of tislelizumab (BGB-A317) plus ociperlimab versus tislelizumab plus placebo as second-line treatment in participants with programmed cell death protein-ligand 1 (PD-L1) tumor area positivity (TAP) ≥ 10% unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Immunosenescence: molecular mechanisms and diseases.
    Liu Z, Liang Q, Ren Y, Guo C, et al · · 2023 · cited 554× · PMID 37179335 · DOI 10.1038/s41392-023-01451-2
  2. Immunotherapy combination approaches: mechanisms, biomarkers and clinical observations.
    Butterfield LH, Najjar YG. · · 2024 · cited 210× · PMID 38057451 · DOI 10.1038/s41577-023-00973-8
  3. TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer.
    Ge Z, Peppelenbosch MP, Sprengers D, Kwekkeboom J. · · 2021 · cited 166× · PMID 34367161 · DOI 10.3389/fimmu.2021.699895
  4. Exploiting innate immunity for cancer immunotherapy.
    Yi M, Li T, Niu M, Mei Q, et al · · 2023 · cited 151× · PMID 38008741 · DOI 10.1186/s12943-023-01885-w
  5. Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials.
    Chu X, Tian W, Wang Z, Zhang J, et al · · 2023 · cited 147× · PMID 37291608 · DOI 10.1186/s12943-023-01800-3
  6. Natural killer cells: a promising immunotherapy for cancer.
    Chu J, Gao F, Yan M, Zhao S, et al · · 2022 · cited 140× · PMID 35606854 · DOI 10.1186/s12967-022-03437-0
  7. Anti-TIGIT therapies for solid tumors: a systematic review.
    Rousseau A, Parisi C, Barlesi F. · · 2023 · cited 111× · PMID 36933320 · DOI 10.1016/j.esmoop.2023.101184
  8. Immune Regulatory Processes of the Tumor Microenvironment under Malignant Conditions.
    Pansy K, Uhl B, Krstic J, Szmyra M, et al · · 2021 · cited 87× · PMID 34948104 · DOI 10.3390/ijms222413311

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