Study of Tislelizumab in Participants With Resectable Esophageal Squamous Cell Carcinoma (RATIONALE-213)

A Phase 2, Multicenter, Open-label, 2-Cohort Study to Investigate the Efficacy and Safety of PET Guided Neoadjuvant Treatment With Tislelizumab (BGB-A317) Plus Chemotherapy/Chemoradiotherapy in Patients With Resectable Esophageal Squamous Cell Carcinoma

The purpose of this study is to evaluate the pathological complete response (pCR) in participants receiving tislelizumab plus chemotherapy/chemoradiotherapy as neoadjuvant treatment.

Study Overview

• Status: Completed
• Conditions: Resectable Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Tislelizumab; Drug: Paclitaxel; Drug: Cisplatin; Procedure: Surgical resection; Drug: 5-fluorouracil; Radiation: Radiotherapy

Detailed Description

This study enrolled participants with esophageal squamous cell carcinoma who were eligible to have their tumor removed by surgery (also called surgical resection). The treatment phase of the study included the following:

• Induction therapy, in which participants received 1 cycle of chemotherapy;

• Neoadjuvant therapy (neoadjuvant refers to treatment that occurs before surgery, which can make the tumor easier to remove). In this study participants received neoadjuvant therapy based on their response to induction therapy. Response to induction therapy was assessed using the maximum standardized uptake value (SUVmax) measured using a Positron Emission Tomography (PET) scan. The SUV number refers to the level of brightness on the PET scan which reflects metabolic activity; increased metabolic activity can indicate cancerous growth.

  • Participants with a decrease in SUVmax of 35% or more after induction therapy received neoadjuvant treatment with tislelizumab plus chemotherapy.
  • Participants with a decrease in SUVmax less than 35% after induction therapy received neoadjuvant treatment with tislelizumab plus chemotherapy and radiotherapy.
• Surgery to remove the remaining tumor (resection) was to occur 4-6 weeks after completion of neoadjuvant treatment.

After surgery participants were followed until death, lost to follow-up, withdrawal of consent, or until the study was completed

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • The Fourth Hospital of Hebei Medical University
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Shaanxi
    • Xi'an, Shaanxi, China, 710038
      • Tangdu Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Eastern Cooperative Oncology Group Performance Status of 0 or 1.
• Histologically confirmed esophageal squamous cell carcinoma (ESCC).
• Stage cT1-2N+M0 and cT3NanyM0 (per The American Joint Committee on Cancer 8th Edition).
• Evaluation by the investigator to confirm eligibility for an R0 resection with curative intent.
• Adequate hematologic and organ function, defined by protocol-specified laboratory test results obtained within 14 days before first dose.

Key Exclusion Criteria:

• Ineligible for treatment with any of the chemotherapy doublets of protocol-specified chemotherapy.
• Any prior therapy for current ESCC, including investigational agents, chemotherapy, radiotherapy, targeted therapy agents, or prior therapy with an anti-programmed cell death protein-1, anti-programmed cell death protein ligand-1, anti-programmed cell death protein ligand-2, or any other antibody or drug specifically targeting T-Cell co-stimulation or checkpoint pathways.
• History of fistula due to primary tumor invasion.
• Participants with high risk of fistula or sign of perforation evaluated by investigator.

• Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days before first dose.

  * Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) and topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption, and short course (≤ 7 days) of corticosteroid prescribed prophylactically or for the treatment of a non-autoimmune condition are permitted.

• Active autoimmune diseases or history of autoimmune diseases that may relapse.

  * Controlled Type I diabetes, hypothyroidism only requiring hormone replacement, controlled celiac disease, skin diseases (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

• History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases.

• With infections requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection.

  • Severe infections within 4 weeks before first dose, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Receive therapeutic oral or intravenous antibiotics within 2 weeks before first dose.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (Responder); Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in positron emission tomography (PET) Standardized Uptake Value (SUV)max ≥ 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and chemotherapy doublet (cisplatin + paclitaxel) for 2 cycles. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.	Drug: Tislelizumab; Administered intravenously on Day 1 of each 21-Day Cycle.; Other Names: BGB-A317; Drug: Paclitaxel; 135 mg/m^2 administered intravenously on Day 1 of each 21-Day Cycle.; Drug: Cisplatin; 80 mg/m^2 administered intravenously on Day 1 of each 21-Day Cycle.; Procedure: Surgical resection; Performed as indicated in the treatment arm.
Experimental: Cohort B (Non-responder); Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in PET SUVmax < 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and investigator-chosen chemotherapy doublet (paclitaxel + cisplatin or 5-fluorouracil + cisplatin) for 2 cycles plus concurrent radiotherapy. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.	Drug: Tislelizumab; Administered intravenously on Day 1 of each 21-Day Cycle.; Other Names: BGB-A317; Drug: Paclitaxel; 135 mg/m^2 administered intravenously on Day 1 of each 21-Day Cycle.; Drug: Cisplatin; 80 mg/m^2 administered intravenously on Day 1 of each 21-Day Cycle.; Procedure: Surgical resection; Performed as indicated in the treatment arm.; Drug: 5-fluorouracil; 1000 mg/m^2 administered intravenously over Day 1 through 4 of each 21-Day Cycle.; Radiation: Radiotherapy; 40 grays/20 fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR) Rate	The pCR rate was defined as the percentage of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes after completion of neoadjuvant treatment. pCR rates were assessed by a pathologist at each site.	pCR was determined from samples taken during surgery; surgery occurred 4-6 weeks after the last dose of chemotherapy, approximately Day 71-86

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 Resection Rate	Defined as the percentage of participants with R0 resection. R0 resection refers to a surgical procedure where the entire tumor is completely removed with no evidence of residual cancer tissue at the surgical margins.	Resection was planned to occur 4-6 weeks after the last dose of chemotherapy, approximately Day 71-86
1-year/3-year Disease-free Survival (DFS) Rate	The DFS rate is defined as the percentage of participants free from disease events at 1 year and 3 years after the first date of no disease (R0 resection as surgery outcome). Disease events include local or distant recurrence or death due to any cause. The DFS rate was analyzed only for participants who underwent R0 resection. Disease-free rates were estimated using the Kaplan-Meier method with 95% confidence intervals estimated using the Greenwood formula.	1 year and 3 years after surgery
1-year/3-year Event-free Survival (EFS) Rate	The EFS rate is defined as the percentage of participants free from EFS events at 1 year and 3 years after the first dose. The EFS events include progression of disease that precludes definitive surgery, local or distant recurrence, or death due to any cause. Event-free rates were estimated using the Kaplan-Meier method with 95% confidence intervals estimated using the Greenwood formula.	1 year and 3 years after first dose date
Objective Response Rate (ORR)	The ORR is defined as the percentage of participants who have a complete response or partial response before surgery as assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in all participants with measurable disease at baseline. Tumor response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) of the neck, chest, and abdomen. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	ORR was assessed prior to surgery, Day 71 to 86
Number Of Participants Experiencing Treatment-Emergent Adverse Events	Immune-mediated AEs were reported until 90 days after the last dose of tislelizumab	From the first dose of study drug up to 30 days after last dose of any component of treatment or surgery or the initiation of subsequent anticancer therapy, whichever occurred first. Up to approximately 9 months.

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2021
• Primary Completion (Actual): April 17, 2023
• Study Completion (Actual): October 25, 2024

Study Registration Dates

• First Submitted: July 3, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Actual): December 1, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: PET; Chemotherapy; Chemoradiotherapy; Tislelizumab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma; Carcinoma, Squamous Cell; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Taxoids; Cyclodecanes; Diterpenes; Pyrimidines; Uracil; Pyrimidinones; Platinum Compounds; Fluorouracil; Paclitaxel; Cisplatin; Radiotherapy; tislelizumab
• Other Study ID Numbers: BGB-A317-213; CTR20211753 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No