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

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of sitravatinib in combination with tislelizumab for the treatment of participants with esophageal squamous cell carcinoma

Official Title
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A 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

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Sitravatinib
* Drug: Tislelizumab
* Drug: Docetaxel
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically or cytologically confirmed locally advanced unresectable or metastatic ESCC, not amenable to treatment with curative intent At least 1 measurable lesion as defined per 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 ECOG PS score ≤ 1 Adequate organ function as indicated by the following laboratory values as indicated by the laboratory tests performed ≤ 7 days before randomization Key Exclusion Criteria: Have any contraindication for receiving treatment with both docetaxel and irinotecan Patients 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) Patients 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 . History of gastrointestinal perforation and/or fistula or aorto-esophageal fistula within 6 months before randomization Have received prior anticancer agents that have same mechanism of action as sitravatinib (eg, RTK inhibitor with a similar target profile or VEGF- or VEGFR-targeted monoclonal antibodies) ther protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Sitravatinib + Tislelizumab<br>Sitravatinib administered orally and tislelizumab administered intravenously | Drug: Sitravatinib<br>* administered orally<br>Drug: Tislelizumab<br>* administered intravenously<br>|
| Experimental: Arm B: Sitravatinib<br>Sitravatinib administered orally | Drug: Sitravatinib<br>* administered orally<br>|
| Experimental: Arm C: Investigator-chosen Chemotherapy<br>Docetaxel or Irinotecan | Drug: Docetaxel<br>* administered intravenously<br>Drug: Irinotecan<br>* administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arms A and C: Overall Response Rate (ORR) | ORR is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | Up to 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | defined as the time from the first confirmed objective response until the first documentation of disease progression or death, whichever comes first | Up to 2 Years | 
| Arms A and C: Overall Survival (OS) | OS is defined as the time from the date of randomization to the date of death due to any cause | Up to 2 Years | 
| Disease Control Rate (DCR) | DCR is defined as the percentage of participants whose best overall response is complete response, partial response, or stable disease, as assessed by the investigator per the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | Up to 2 Years | 
| Clinical Benefit Rate (CBR) | CBR is defined as the percentage of participants who have complete response, partial response, and stable disease, as assessed by the investigator per the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | Up to 2 Years | 
| Progression Free Survival (PFS) | PFS is defined as the time from the date of randomization until first documentation of progression or death, whichever comes first, as assessed by the investigator Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | Up to 2 Years | 
| Overall Response Rate (ORR) as assessed by the investigator | defined as the proportion of patients with a confirmed complete response or partial response per RECIST v1.1 | Up to 2 Years | 
| Number of participants with adverse events (AEs) | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) | Up to 2 Years | 
| Number of participants with clinically significant changes from baseline in clinical laboratory values | Laboratory values include hematology, clinical chemistry, coagulation, and urinalysis | Up to 2 Years | 
| Number of participants with clinically significant changes from baseline in vital signs | Vital signs include blood pressure and pulse rate | Up to 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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esophageal squamous cell carcinoma