Study To Investigate the Efficacy and Safety of Sitravatinib in Combination With Tislelizumab in Participants With Esophageal Squamous Cell Carcinoma

Phase 2, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sitravatinib in Combination With Tislelizumab in Patients With Locally Advanced Unresectable or Metastatic Esophageal Squamous Cell Carcinoma That Progressed on or After Anti-PD-(L)1 Antibody Therapy

The study aimed to evaluate the efficacy and safety of sitravatinib in combination with tislelizumab as a second- or third-line treatment for participants with locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma (ESCC) who experienced disease progression following prior systemic chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Sitravatinib; Drug: Tislelizumab; Drug: Docetaxel; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230088
      • Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital
    • Hefei, Anhui, China, 230036
      • Anhui Provincial Hospital South Brance
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 101149
      • Beijing LuHe Hospital, Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
    • Fuzhou, Fujian, China, 350005
      • The First Affiliated Hospital of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat Sen University Cancer Center
    • Guangzhou, Guangdong, China, 510700
      • Sun Yat Sen University Cancer Center(Huangpu Campus)
    • Shantou, Guangdong, China, 515031
      • Cancer Hospital of Shantou University Medical College
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The Tumor Hospital Affiliated to Guangxi Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Xinxiang, Henan, China, 453100
      • The First Affiliated Hospital of Xinxiang Medical University
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Xiangyang, Hubei, China, 441021
      • Xiangyang Central Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Jiangsu
    • Yangzhou, Jiangsu, China, 225001
      • Northern Jiangsu Peoples Hospital
  • Jiangxi
    • Ganzhou, Jiangxi, China, 341000
      • Ganzhou Peoples Hospital Ganzhou Hospital Affiliated to Nanchang University
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • Jilin
    • Changchun, Jilin, China, 130021
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital and Institute
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Weifang, Shandong, China, 261000
      • Weifang Peoples Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China, 610071
      • Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Histologically or cytologically confirmed locally advanced unresectable or metastatic ESCC, not amenable to treatment with curative intent
2. At least 1 measurable lesion as defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by local site investigator/radiology assessment ≤ 28 days before randomization Note: Lesions that had been previously irradiated were considered evaluable provided
3. Eastern Cooperative Oncology Group (ECOG) score ≤ 1
4. Adequate organ function as indicated by the following laboratory values as indicated by the laboratory tests performed ≤ 7 days before randomization

Key Exclusion Criteria:

1. Have any contraindication for receiving treatment with both docetaxel and irinotecan
2. Participants with tumor located around important vascular structures as shown by imaging or the investigator determines that the tumor is likely to invade important blood vessels and may cause fatal bleeding (ie, radiologic evidence of tumors invading or abutting major blood vessels)
3. Participants with tumor that invades into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) that has an increased risk of fistula during the study treatment period as assessed by the investigator
4. History of gastrointestinal perforation and/or fistula or aorto-esophageal fistula within 6 months before randomization
5. Have received prior anticancer agents that have same mechanism of action as sitravatinib (eg, receptor tyrosine kinases (RTKs) with a similar target profile or Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor-targeted (VEGFR) monoclonal antibodies)

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm B: Sitravatinib; Sitravatinib administered orally	Drug: Sitravatinib; 100 mg orally once daily; Other Names: BGB-9468
Experimental: Arm A: Tislelizumab + Sitravatinib; Sitravatinib administered orally and tislelizumab administered intravenously	Drug: Sitravatinib; 100 mg orally once daily; Other Names: BGB-9468; Drug: Tislelizumab; 200 mg intravenously once every 3 weeks; Other Names: BGB-A317
Experimental: Arm C: Investigator-chosen chemotherapy (ICC); Investigators chose between docetaxel or irinotecan	Drug: Docetaxel; 75 milligrams per square meter of body surface area (mg/m2) intravenously on Day 1 of every 21-day cycle; Drug: Irinotecan; 125 mg/m2 intravenously on Days 1 and 8 of every 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arms A and C: Overall Response Rate (ORR)	ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as assessed by the investigator per the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1.	Through study completion data cut-off date of February 26th, 2024 (maximum time on study was 12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	Defined as the time from the first occurrence of a documented objective response to the time of documented disease progression assessed by the investigator or death from any cause, whichever occurred first, in all randomized participants with documented objective responses.	Through study completion data cut-off date of February 26th, 2024 (maximum time on study was 12 months)
Overall Survival (OS)	Defined as the time from randomization until the date of death due to any cause. Kaplan-Meier methodology was used to estimate the median OS.	Through study completion data cut-off date of February 26th, 2024 (maximum time on study was 12 months)
Disease Control Rate (DCR)	Defined as the percentage of participants whose best overall response is complete response, partial response, or stable disease, as assessed by the investigator per RECIST v1.1	Through study completion data cut-off date of February 26th, 2024 (maximum time on study was 12 months)
Clinical Benefit Rate (CBR)	Defined as the percentage of participants with a complete response, partial response, or durable stable disease (defined as stable disease for 24 weeks or longer, as assessed by the investigator per RECIST v.1.1.	Through study completion data cut-off date of February 26th, 2024 (maximum time on study was 12 months)
Progression Free Survival (PFS)	Defined as the time from randomization until first documentation of disease progression as assessed by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. Kaplan-Meier methodology was used to estimate the median PFS.	Through study completion data cut-off date of February 26th, 2024 (maximum time on study was 12 months)
Arms A and B: Overall Response Rate (ORR)	ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as assessed by the investigator per RECIST v1.1. Analysis of ORR in Arm A compared to Arm B was specified as a secondary endpoint in the Protocol (please see the primary outcome measure for Arm C results)	Through study completion data cut-off date of February 26th, 2024 (maximum time on study was 12 months)
Number of Participants With Adverse Events	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, and vital signs, according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0	From the first dose to 30 days after the last dose or the start of new anticancer therapy, whichever occurred first (maximum time on treatment was 8.9 months for Arm A, 7.7 months for Arm B, and 8.0 months for Arm C).

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Actual): February 26, 2024
• Study Completion (Actual): February 26, 2024

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: esophageal squamous cell carcinoma
• 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; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Docetaxel; Irinotecan; Tislelizumab
• Other Study ID Numbers: BGB-A317-Sitravatinib-203; CTR20222088 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No