Tislelizumab as Single-Agent Neoadjuvant Immunotherapy in Resectable Esophageal Squamous Cell Carcinoma

Tislelizumab as Single-Agent Neoadjuvant Immunotherapy in Resectable Esophageal Squamous Cell Carcinoma: A Single-Arm, Phase II Clinical Study（TISNEOS）

Tislelizumab in resectable esophageal squamous cell carcinoma

Study Overview

• Status: Not yet recruiting
• Conditions: Esophagus Cancer
• Intervention / Treatment: Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years old ≤75 years old, male or female;
• T2-3N0-+M0 or T1bN+M0 thoracic esophageal squamous cell carcinoma (as defined in AJCC 8th Edition) with a definite gastroscopic biopsy.
• There is at least one measurable lesion (RECIST1.1 standard);
• ECOG PS 0~1;
• Expected survival ≥ 12 months;
• Newly diagnosed patients who have not received surgery, chemoradiotherapy, targeted therapy, immunotherapy and other treatments before;
• Women of childbearing age must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment. Male subjects and women of reproductive age must be on contraception within 24 weeks of starting the first study drug and the last study drug.

• The laboratory test value of the patient before medication shall meet the following criteria:

  1. Blood routine: WBC≥3.0 × 109/L; ANC≥1.5 × 109/L; PLT≥100 × 109/L; HGB≥ 9.0g /dL
  2. Liver function: AST≤2.5 × ULN, ALT≤2.5 × ULN, TBIL≤1.5 × ULN
  3. Renal function: Cr≤1.5 × ULN or CrCl ≥50 mL/min
  4. Coagulation function: INR≤1.5, APTT≤1.5 ×ULN;
• Subjects voluntarily joined the study, signed informed consent, had good compliance, and cooperated with follow-up.

Exclusion Criteria:

• Esophageal adenocarcinoma was confirmed by histological or cytological pathology;
• Previous T cell co-stimulation or immune checkpoint therapy, including but not limited to CTLA-4 inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other T cell-targeting drugs;
• A previous or current history of cancer other than esophageal cancer, other than non-melanoma skin cancer that has been treated therapeutically, cervical cancer in situ, or other cancer that has been treated therapeutically and has not shown signs of recurrence for at least 5 years;
• Interstitial lung disease, drug-induced pneumonia, radiation pneumonia requiring steroid treatment or active pneumonia with clinical symptoms or severe lung dysfunction;
• Uncontrolled hypertension with standard treatment (blood pressure not stabilized below < 150/90 mmHg);
• Hereditary bleeding tendency or coagulation dysfunction. There were clinically significant bleeding symptoms or definite bleeding tendencies within 3 months prior to enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, stool occult blood ++ or above at baseline;
• Have clinical symptoms or diseases of heart that are not well controlled, such as: (1) NYHA2 or higher heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 24 weeks, (4) clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention;
• Severe infections (CTCAE > Class 2), such as severe pneumonia requiring hospitalization, bacteremia, and infection complications, occurred within 4 weeks prior to the first use of the study drug;
• Patients with clinically uncontrollable third space effusion (such as pleural effusion/pericardial effusion, who do not need to drain the effusion or have no significant increase in effusion after 3 days of stopping drainage can be included in the group);
• Imaging (CT or MRI) shows that the tumor has invaded the major blood vessels, or the investigator determines that the tumor is highly likely to invade important blood vessels and cause fatal massive bleeding during the follow-up study;
• A history of immunodeficiency, including HIV testing positive, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation and allogeneic bone marrow transplantation;
• Patients with active hepatitis B (defined as positive HBV surface antigen [HBsAg] test result during screening and HBV-DNA test value higher than the upper limit of normal value in the laboratory of the research center) or hepatitis C (defined as positive HCV surface antibody [HCsAb] test result during screening and HCV-RNA positive);
• Those who have allergic reaction to the experimental drug used in this application;
• According to the investigator's judgment, the subjects have other factors that may lead to the forced termination of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab	Drug: Tislelizumab; Tislelizumab 200mg Q3W, D1 ; 2 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response	Total tumor regression rate under pathologyPrimary tumor or lymph node surgery specimen pathological examination without residual tumor cell	4 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathological response	Total/moderate tumor regression rate under pathologyPrimary tumor or lymph node surgery specimen pathological examination without residual tumor cell	4 weeks after surgery
Objective Response Rate	Determine the tumor shrinkage rate, tumor boundary and the adhesion of tumor	At the end of Cycle 2 (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2025
• Primary Completion (Estimated): January 10, 2026
• Study Completion (Estimated): January 10, 2027

Study Registration Dates

• First Submitted: November 12, 2024
• First Submitted That Met QC Criteria: November 15, 2024
• First Posted (Actual): November 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 26, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• 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; Carcinoma; Neoplasms, Squamous Cell; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Carcinoma, Squamous Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Tislelizumab
• Other Study ID Numbers: TISNEOS

Drug and device information, study documents

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