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

BeiGene649 enrolled

Overview

The purpose of this study is to evaluate the efficacy and safety of tislelizumab as first line treatment in combination with chemotherapy in participants with advanced unresectable/metastatic esophageal squamous cell carcinoma (ESCC).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

649

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)

Interventions

CisplatinDRUG

Cisplatin 60-80 mg/m² administered by intravenous infusion every 3 weeks. Cisplatin was used as the platinum agent in China, Taiwan, and Japan.

OxaliplatinDRUG

Oxaliplatin 130 mg/m² administered by intravenous infusion every 3 weeks.

Fluorouracil (5-FU)DRUG

Fluorouracil 750-800 mg/m² administered by intravenous infusion on Days 1-5 of each treatment cycle.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Pathologically (histologically) confirmed diagnosis of ESCC 2. Stage IV unresectable ESCC at first diagnosis OR unresectable, locally advanced recurrent or metastatic disease (per American Joint Committee on Cancer 7th Edition), if there is prior neoadjuvant/adjuvant therapy with platinum-based chemotherapy, a treatment-free interval of at least 6 months is required. Key Exclusion Criteria: 1. Palliative radiation treatment for ESCC within 4 weeks of study treatment initiation 2. Prior systemic therapy for unresectable, locally advanced recurrent or metastatic ESCC 3. Received prior therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1) or PD-L2 4. Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta) 5. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (clinically significant recurrence requiring an additional intervention within 2 weeks of intervention) 6. Evidence of complete esophageal obstruction not amenable to treatment 7. Unintentional weight loss ≥ 5% within one month prior to randomization or Nutritional Risk Index (NRI) \< 83.5 per investigator's choice 8. Locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy per local investigator. 9. Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is ≥ 500 IU/mL or participants with active hepatitis C virus (HCV) NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (124)

Outcomes

Primary Outcomes

Overall Survival (OS)

Overall survival is defined as the time from the date of randomization until the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method. Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority.

Time frame: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.

Secondary Outcomes

Progression-Free Survival (PFS)

Progression-free survival is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or unequivocal progression of existing nontarget lesions, or the appearance of 1 or more new lesions. Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.

Time frame: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.

Objective Response Rate (ORR)

ORR is defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) assessed by the investigator per RECIST v1.1. Tumor assessments included computed tomography (CT) scans or magnetic resonance imaging (MRI), with preference for CT, of the neck, chest, and abdomen. CR: Disappearance of all target and nontarget lesions with no new lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: Disappearance of all target lesions with persistence of 1 or more nontarget lesion(s), no new lesions, and/or maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis (data cutoff date of 28 February 2022).

Data from ClinicalTrials.gov

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Capecitabine 1000 mg/m² administered orally twice daily on Days 1-14 of each treatment cycle

PaclitaxelDRUG

Paclitaxel 175 mg/m² administered by intravenous infusion every 3 weeks.

TislelizumabBIOLOGICAL

Tislelizumab 200 mg administered by intravenous infusion every 3 weeks.

PlaceboDRUG

Placebo to match tislelizumab administered by intravenous infusion every 3 weeks.

Smilow Cancer Hospital At Yale

New Haven, Connecticut, United States

Renovatio Clinical

The Woodlands, Texas, United States

Coffs Harbour Base Hospital

Coffs Harbour, New South Wales, Australia

St Vincents Hospital Melbourne

Fitzroy, Victoria, Australia

Institut Jules Bordet

Anderlecht, Belgium

Az Sint Jan Brugge

Bruges, Belgium

Grand Hopital de Charleroi Site Notre Dame

Charleroi, Belgium

UZ GENT

Ghent, Belgium

University Hospitals Leuven

Leuven, Belgium

Chc Montlegia

Liège, Belgium

...and 114 more locations

Time frame: Response was assessed every 6 weeks for the first 48 weeks, then every 9 weeks thereafter; up to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.

Overall Survival (OS) in Participants With a PD-L1 Score ≥ 10%

OS is defined as the time from the date of randomization until the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method. Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.

Time frame: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.

Duration of Response (DOR)

DOR is defined as the time from the first determination of an objective response until the first documentation of progression assessed by the investigator per RECIST v1.1 or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.

Time frame: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.

Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Oesophageal Cancer 18 Question Module (QLQ-OES18) Dysphagia, Eating, Reflux, Pain, and Index Scores

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

Time frame: Baseline, Cycle 6 (Week 15)

Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) and Physical Functioning Scales

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.

Time frame: Baseline, Cycle 6 (Week 15)

Change From Baseline in EORTC QLQ-C30 Fatigue Scale

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.

Time frame: Baseline, Cycle 6 (Week 15)

Change From Baseline in European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Visual Analog Scale (VAS)

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.

Time frame: Baseline, Cycle 6 (Week 15)

Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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.

Time frame: From first dose of study drug up to 30 days after last dose; maximum time on treatment was 63.5 months.