Esophageal Squamous Cell Carcinoma (ESCC)
Conditions
Brief summary
This is a phase 3, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of tislelizumab (BGB-A317) versus placebo in combination with chemoradiotherapy in participants with localized esophageal squamous cell carcinoma (ESCC).
Interventions
DRUGTislelizumab
Administered intravenously (IV)
DRUGPlacebo
Placebo to match tislelizumab administered intravenously
DRUGPaclitaxel
Administered as 135 mg/m² IV injection
DRUGCisplatin
Administered as 25 mg/m² IV injection
RADIATIONRadiotherapy
Administered at a total dose of 50.4 Gy in 28 fractions
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically confirmed diagnosis of localized ESCC and suitable for concurrent chemoradiotherapy (cCRT) * Measurable and/or non-measurable disease defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 * Adequate organ function Key
Exclusion criteria
* Indicators of severe malnutrition * Clinically uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention within 2 weeks prior to randomization * Known to be intolerable or resistant to treatment with the protocol-specified chemotherapy * Received prior radiotherapy or therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1), PD-L2 or other immune-oncology therapies * Active autoimmune diseases or history of autoimmune diseases that may relapse NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | From randomization to the prespecified primary analysis data cut-off date of 08 January 2025; maximum time on study was 67 months. | PFS is defined as the time from randomization to the first documented disease progression, as determined by the Blinded Independent Review Committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death from any cause, whichever occurred first. PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): 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, and/or unequivocal progression of existing nontarget lesions. or the appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization to the prespecified analysis data cut-off date of 08 January 2025; maximum time on study was 67 months. | OS is defined as the time from the date of randomization to the date of death due to any cause. OS was estimated using the Kaplan-Meier method. |
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Oesophageal Cancer Module (OES18) Dysphagia, Reflux, Pain, and Eating Scales | Baseline and Cycle 6 and Cycle 10 (each cycle was 21 days) | 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. |
| Change From Baseline in EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL), Physical Functioning, and Fatigue Scores | Baseline and Cycle 6 and Cycle 10 (each cycle was 21 days) | 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 into a 0 to 100 scale via linear transformation. Higher scores in GHS and functional scales indicate better quality of life. Lower scores in symptom scales indicate better quality of life. |
| Overall Response Rate (ORR) | Tumor assessments occurred every 9 weeks for the first 54 weeks, and every 12 weeks during the next 2 years and every 24 weeks thereafter until radiographic disease progression or death; up to 67 months | ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by BIRC per RECIST v1.1. Tumor assessments were made using computed tomography (CT) scans or using magnetic resonance imaging (MRI). CR: Disappearance of all target lesions and non-target lesions, no new lesions, and normalization of tumor marker level. All lymph nodes must be nonpathological in size (\<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and/or persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. |
| Duration of Response (DOR) | Up to 67 months | DOR is defined as the time from the first occurrence of a documented objective response to the time of relapse, as determined by the BIRC per RECIST v1.1, or death from any cause, whichever occurs first. DOR was estimated using the Kaplan-Meier method. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug to 30 days after last dose, maximum time on treatment was 57.5 months | An adverse event (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 a study treatment, whether considered related to study treatment or not. A TEAE is an AE that had an onset date or a worsening in severity from baseline on or after the first dose of study treatment and up to 30 days following study treatment discontinuation or initiation of new anticancer therapy, whichever occurred first. A serious adverse event (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. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORWeihu Wang, MD
Peking University Cancer Hospital & Institute
PRINCIPAL_INVESTIGATORZefen Xiao, MD
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Participant flow
Recruitment details
This study was conducted at 32 centers in China.
Pre-assignment details
Eligible participants were randomized in a 1:1 ratio to receive either tislelizumab or placebo in combination with concurrent chemoradiotherapy (cCRT).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 200 Participants |
| Age, Categorical Between 18 and 65 years | 170 Participants |
| Age, Continuous | 65.0 years |
| Clinical Stage Stage II | 44 Participants |
| Clinical Stage Stage III | 96 Participants |
| Clinical Stage Stage IVa | 45 Participants |
| Clinical Stage Stage IVb | 1 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully Active) | 78 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Ambulatory with Restricted Activity) | 107 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 185 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 161 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 100 / 185 | 93 / 185 |
| other Total, other adverse events | 185 / 185 | 184 / 184 |
| serious Total, serious adverse events | 84 / 185 | 63 / 184 |
Outcome results
None listed