A Study to Investigate Tislelizumab (BGB-A317) Versus Placebo in Combination With Concurrent Chemoradiotherapy in Participants With Localized Esophageal Squamous Cell Carcinoma

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• Esophageal Squamous Cell Carcinoma 645

Esophageal Squamous Cell Carcinoma

645 studies on the registry are indexed under Esophageal Squamous Cell Carcinoma; 275 are open to participants now.

This study's enrollment of 370 is above the median of 65 across 539 interventional studies indexed under Esophageal Squamous Cell Carcinoma.

Lead sponsor

BeiGene is the lead sponsor of 122 studies on the registry; 3 are open to participants now.

Of its 52 completed or terminated interventional studies of FDA-regulated products, 31 (60%) have results posted.

Eligibility criteria

Study arms

• Experimental
  Tislelizumab + Chemoradiotherapy

  Participants received 200 mg tislelizumab administered intravenously (IV) once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by 200 mg tislelizumab for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first. Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).

  Drug: Tislelizumab · Drug: Paclitaxel · Drug: Cisplatin · Radiation: Radiotherapy

• Placebo comparator
  Placebo + Chemoradiotherapy

  Participants received placebo IV once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by placebo for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first. Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).

  Drug: Placebo · Drug: Paclitaxel · Drug: Cisplatin · Radiation: Radiotherapy

Interventions

• DrugTislelizumab

  Administered intravenously (IV)

  Also known as: BGB-A317, Tevimbra

• 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

Primary outcomes

1. Progression-free Survival (PFS)

   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.

   Time frame: From randomization to the prespecified primary analysis data cut-off date of 08 January 2025; maximum time on study was 67 months.

Secondary outcomes

1. Overall Survival (OS)

   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.

   Time frame: From randomization to the prespecified analysis data cut-off date of 08 January 2025; maximum time on study was 67 months.

2. 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

   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.

   Time frame: Baseline and Cycle 6 and Cycle 10 (each cycle was 21 days)

3. 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

   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.

   Time frame: Baseline and Cycle 6 and Cycle 10 (each cycle was 21 days)

4. Overall Response Rate (ORR)

   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.

   Time frame: 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

5. Duration of Response (DOR)

   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.

   Time frame: Up to 67 months

6. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

   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.

   Time frame: From first dose of study drug to 30 days after last dose, maximum time on treatment was 57.5 months

Baseline characteristics

Publications

• Yu R, Wang W, Li T, Li J, Zhao K, Wang W, Liang L, Wu H, Ai T, Huang W, Li L, Yu W, Wei C, Wang Y, Shen W, Xiao Z. RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma. Future Oncol. 2021 Nov;17(31):4081-4089. doi: 10.2217/fon-2021-0632. Epub 2021 Jul 16. PubMed 34269067 ↗

Study documents

• Study protocol · Sep 30, 2024
• Statistical analysis plan · Nov 14, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

Supporting information: Study protocol, Sap, Csr