Adebrelimab Plus Full-course Neoadjuvant Therapy for Resectable Locally Advanced ESCC (Phase 2) (NAT-ESCC-01)

A Prospective, Single-Center, Phase II Clinical Trial of Adebrelimab Combined With Full-Course Neoadjuvant Therapy for Watchful Waiting or Surgery in Patients With Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

This is a prospective, single-center, randomized phase 2 study of adebrelimab plus full-course neoadjuvant therapy in resectable locally advanced esophageal squamous cell carcinoma. Patients achieving clinical complete response (cCR) after neoadjuvant treatment will be randomized 1:1 to watchful waiting with 2 cycles consolidation chemo-Immunotherapy or standard surgery. Primary endpoint is 2-year DFS. Secondary endpoints include OS, pCR/MPR, R0 resection rate, safety, and quality of life.

Study Overview

• Status: Not yet recruiting
• Conditions: ESCC
• Intervention / Treatment: Drug: Combination therapy with chemotherapy and immunotherapy; Other: Surgery

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Tang Peng Tang; Phone Number: +8618622228653; Email: 18526812877@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients voluntarily participate in this study, sign an informed consent form, and demonstrate good compliance;
• At least 18 years of age; gender is not restricted;
• ECOG performance status: 0-1;
• Patients with histologically confirmed resectable esophageal squamous cell carcinoma clinically staged as (T1N+M0 or T2-4aNanyM0);
• No prior anticancer therapy for esophageal cancer, including chemotherapy, hormone therapy, radiation therapy, or immunotherapy;

• Laboratory tests must meet the following criteria (within 7 days prior to baseline enrollment):

  1. Complete blood count (CBC):

     1. Hemoglobin (Hb) ≥ 90 g/L (no blood transfusion within the past 14 days);
     2. Neutrophil count (NEUT) ≥ 1.5 × 10⁹/L;
     3. Platelet count (PLT) ≥ 100 × 10⁹/L;
     4. White blood cell count (WBC) ≥ 3 × 10⁹/L;

  2. Biochemical Tests:

     1. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5×ULN;
     2. Serum total bilirubin (TBIL) ≤ 1.5×ULN;
     3. Serum creatinine (Cr) ≤ 1.5×ULN; (or creatinine clearance (CCr) ≥ 60 mL/min);
  3. Coagulation function: Activated partial thromboplastin time (APTT), International Normalized Ratio (INR), and prothrombin time (PT) ≤ 1.5×ULN;
  4. Thyroid function: Thyroid-stimulating hormone (TSH) ≤ ULN (if abnormal, FT3 and FT4 levels should also be evaluated; if FT3 and FT4 levels are normal, the patient may be enrolled);
  5. Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%;
• Female participants must agree to use contraceptive measures, such as an intrauterine device (IUD), oral contraceptives, or condoms, during the study and for 6 months after study completion; they must have a negative serum pregnancy test within 7 days prior to study enrollment and must not be breastfeeding; male participants must agree to use contraceptive measures during the study and for 6 months after study completion.

Exclusion Criteria:

• Concurrent malignant neoplasms (except for cured basal cell carcinoma of the skin);
• Diagnosis of cervical esophageal cancer;
• History of severe hypersensitivity reactions following administration of other monoclonal antibodies;
• Presence of any active autoimmune disease or history of autoimmune disease (such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, or nephritis; asthma requiring bronchodilators for medical intervention); however, the following patients are eligible for enrollment: vitiligo, psoriasis, or alopecia not requiring systemic treatment; well-controlled type 1 diabetes; hypothyroidism with normal thyroid function following replacement therapy;
• Requiring immunosuppressants, or systemic or absorbable topical corticosteroids for immunosuppressive purposes (dose > 10 mg/day of prednisone or other corticosteroids of equivalent potency), and still using them within 2 weeks of the first dose;
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• Uncontrolled symptoms of brain metastases, spinal cord compression, or carcinomatous meningitis occurring within 4 weeks prior to the first dose, or patients with brain or meningeal disease identified by CT or MRI at screening;

• Patients with any severe and/or uncontrolled medical conditions, including:

  1. Acute or recurrent myocardial ischemia or myocardial infarction; poorly controlled and clinically significant arrhythmias; and heart failure of Class II or higher (New York Heart Association [NYHA] functional class); LVEF (left ventricular ejection fraction) < 50%;
  2. Active or uncontrolled severe infection (≥ Grade 2 CTC AE infection);
• Receipt of a prophylactic or attenuated vaccine within 4 weeks prior to the first dose;
• Other factors, as determined by the investigator, that may lead to forced discontinuation of the study, such as other serious illnesses (including psychiatric disorders) requiring concomitant treatment, severe laboratory abnormalities, or family or social factors that could compromise the subject's safety.
• If HBsAg (+) and/or HBcAb (+), HBV DNA must be < 500 IU/mL (if the local center's lower limit of detection is higher than 500 IU/mL, the investigator may decide on enrollment based on specific circumstances) and the subject must continue to receive effective anti-HBV therapy during the study, or must have already started treatment with entecavir or tenofovir prior to study drug administration;
• If HCV antibodies are positive, HCV-RNA testing must be performed; subjects with HCV-RNA > 10³ copies/mL must be excluded;
• HIV-positive.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Surgery	Other: Surgery; surgery
Experimental: Combination therapy with chemotherapy and immunotherapy	Drug: Combination therapy with chemotherapy and immunotherapy; Adebrelimab Injection，intravenous infusion, Day 1, every 3 weeks for 2 cycles. Albumin-bound paclitaxel 260 mg/m², carboplatin AUC = 5, intravenous infusion, Day 1, every 3 weeks for 2 cycles. Two cycles of chemotherapy combined with immunotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year Disease-Free Survival (DFS) rate in the watchful waiting arm	Assessed from randomization to disease recurrence, progression, or death, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Overall Survival (OS) in the watchful waiting arm		From randomization to death, up to 2 years
2-year OS in the surgery arm		From randomization to death, up to 2 years
R0 resection rate		Assessed at surgery
Pathological Complete Response (pCR) rate		Assessed at surgery
Major Pathological Response (MPR) rate		Assessed at surgery
Event-Free Survival (EFS)		From enrollment to progression/recurrence/death, up to 2 years
Clinical Complete Response (cCR) rate	Assessed after completion of neoadjuvant therapy, prior to surgical resection.	Within 1-2 weeks prior to surgery, after completion of neoadjuvant therapy.
EORTC QLQ-C30 Quality of Life Score	Assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). The scale ranges from 0 to 100, with higher scores indicating better quality of life for functional scales and worse symptoms for symptom scales.	Baseline, 6 months, 12 months, 24 months
Treatment Completion Rate	The proportion of patients who complete the planned neoadjuvant therapy regimen as defined in the protocol.	From first study treatment to end of neoadjuvant therapy,Evaluation period: up to 12 months.
Adverse Event (AE) and Serious Adverse Event (SAE) Incidence (CTCAE v6.0)	Incidence of all adverse events (AEs) and serious adverse events (SAEs) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.	From first study treatment to 30 days after last study treatment.

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 9, 2026
• First Submitted That Met QC Criteria: May 7, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Biological Therapy; Immunomodulation; Combined Modality Therapy; Drug Therapy; Surgical Procedures, Operative; Immunotherapy
• Other Study ID Numbers: NAT-ESCC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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