Tislelizumab plus chemotherapy to convert unresectable locally advanced esophageal squamous cell carcinoma to surgery

Efficacy and Safety of Tislelizumab Plus Chemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma

This study will try whether adding the immune drug tislelizumab to chemotherapy can shrink tumors so people with initially unresectable locally advanced esophageal squamous cell carcinoma can become eligible for surgery.

Quick facts

• Study type: Observational
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shandong Provincial Hospital (Government)
• Drugs / interventions: tislelizumab, chemotherapy, prednisone
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT07549100 on ClinicalTrials.gov

What this trial studies

This is a single-arm, single-center, open-label observational study enrolling 30 patients with initially unresectable locally advanced esophageal squamous cell carcinoma. Eligible participants receive albumin-bound paclitaxel plus cisplatin or carboplatin together with tislelizumab for 2–4 cycles, followed by tumor restaging. A multidisciplinary team will determine whether tumors have shrunk enough to allow surgical resection. The primary outcome is the conversion rate to surgery, with secondary outcomes including pathological complete response, objective response rate, and safety.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed thoracic esophageal squamous cell carcinoma that is initially unresectable locally advanced (T4b invasion or bulky/multistation nodal disease), no distant metastases, ECOG 0–1, at least one measurable lesion, and adequate organ function are ideal candidates.

Not a fit: Patients with distant metastatic disease, poor performance status, inadequate organ function, non-squamous histology, or who cannot tolerate platinum-based chemotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could allow some patients with previously unresectable disease to undergo potentially curative surgery and improve long-term outcomes.

How similar studies have performed: PD-1 inhibitors combined with chemotherapy have improved response rates in esophageal cancer in other studies, but using tislelizumab specifically as conversion therapy for unresectable locally advanced ESCC is less well established.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent is obtained prior to any study-related procedures.
2. Age 18 to 75 years, inclusive; both male and female patients are eligible.
3. Histologically and radiologically confirmed thoracic esophageal squamous cell carcinoma (ESCC) with initially unresectable locally advanced disease, defined as:

   T4b tumors invading adjacent critical structures, including the heart, great vessels, trachea, or other adjacent organs (including liver, pancreas, lung, or spleen); or Multiple-station or bulky lymph node metastases.
4. No evidence of distant metastasis.
5. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Estimated life expectancy of ≥6 months.
8. Adequate organ function, as defined below (without transfusion of blood products or use of hematopoietic growth factors within 14 days prior to assessment):

   Hematologic function: absolute neutrophil count (ANC) ≥1,500/mm³; platelet count ≥100,000/mm³; hemoglobin ≥9 g/dL (5.6 mmol/L).

   Renal function: serum creatinine ≤1.5 mg/dL and/or creatinine clearance ≥60 mL/min.

   Hepatic function: total bilirubin ≤1.5 × upper limit of normal (ULN); AST and ALT ≤1.5 × ULN.
9. For women of childbearing potential: must have a negative serum or urine pregnancy test within 7 days prior to enrollment, must not be breastfeeding, and must agree to use a medically acceptable method of contraception (e.g., intrauterine device, oral contraceptives, or barrier methods) during the study treatment period and for at least 3 months after the last dose.

   For men with partners of childbearing potential: must agree to use a medically acceptable method of contraception during the study treatment period and for at least 3 months after the last dose.
10. Willingness to participate in the study, good compliance, and ability to adhere to study procedures, including safety and survival follow-up.

Exclusion Criteria:

1. Prior receipt of radiotherapy, chemotherapy, hormonal therapy, surgery, or molecular targeted therapy for esophageal cancer.
2. Evidence of distant metastasis confirmed by imaging.
3. History of other malignancies, except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.
4. Prior treatment with any anti-PD-1 or anti-PD-L1 agents; known hypersensitivity to monoclonal antibodies or any component of tislelizumab.
5. Active autoimmune disease or a history of autoimmune disease, including but not limited to autoimmune hepatitis, interstitial lung disease, uveitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism.
6. Patients with vitiligo or a history of childhood asthma that has completely resolved and requires no intervention in adulthood may be eligible.
7. Patients with asthma requiring bronchodilator therapy are not eligible.
8. Current use of immunosuppressive medications, including systemic corticosteroids or absorbable local steroids for immunosuppressive purposes (dose \>10 mg/day prednisone or equivalent) within 2 weeks prior to enrollment.

   Clinically significant ascites or pleural effusion requiring therapeutic drainage.

   Uncontrolled or clinically significant cardiovascular disease, including but not limited to:

   New York Heart Association (NYHA) class II or higher heart failure; Unstable angina; Myocardial infarction within 1 year prior to enrollment; Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
9. Coagulation abnormalities, defined as: prothrombin time (PT) \>16 seconds, activated partial thromboplastin time (APTT) \>43 seconds, thrombin time (TT) \>21 seconds, or fibrinogen (Fbg) \>2 g/L; or presence of bleeding tendency, or ongoing thrombolytic or anticoagulant therapy.
10. Presence of gastrointestinal conditions associated with a high risk of bleeding or perforation within 3 months prior to enrollment, including but not limited to esophageal varices, active gastric or duodenal ulcers, ulcerative colitis, portal hypertension, or unresected tumors with active bleeding; or any other condition judged by the investigator to pose a risk of gastrointestinal bleeding or perforation.

Where this trial is running

Jinan, Shandong

• Shandong Provincial Hospital — Jinan, Shandong, China (Recruiting)

Study contacts

• Study coordinator: ALei Feng

Conditions Locally Advanced Esophageal Squamous Cell Carcinoma