Active Surveillance After Neoadjuvant Adebrelimab Combined With Chemoradiotherapy for Resectable ESCC

Active Surveillance After Neoadjuvant Adebrelimab Combined With Chemoradiotherapy for Resectable Esophageal Squamous Cell Carcinoma

In this prospective trial, patients demonstrating clinical complete response (cCR) as determined by a standard response assessment protocol (incorporating clinical and molecular diagnostic methods) will be offered organ-sparing management following neoadjuvant therapy with adebrelimab (anti-PD-L1) concurrent with chemoradiotherapy. The primary endpoint is 2-year overall survival rate in this watch-and-wait cohort.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Adebrelimab and nab-paclitaxel and carboplatin; Radiation: Radiation; Procedure: standard oesophagectomy; Other: active surveillance

• Study Type: Interventional
• Enrollment (Estimated): 164
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhigang Li, MD, PhD; Phone Number: 86-18960619260; Email: zhigang.li@shsmu.edu.com
• Study Contact Backup: Name: Zhichao Liu, MD, PhD; Phone Number: 86-15622175948; Email: zhichao.liu@sjtu.edu.cn

Study Locations

• China
  • Shanghai, China
    • Shanghai Chest Hospital
    • Contact: Zhigang Li, MD, PhD; Phone Number: 18960619260; Email: zhigang.li@shsmu.edu.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects signed the informed consent and volunteered to participate in the study.
2. Esophageal squamous cell carcinoma confirmed by histology or cytology.
3. Thoracic esophageal squamous cell carcinoma confirmed by CT or pet-CT, which is classified as cII-III (AJCC 8th).
4. Expect to have R0 resection
5. In age from 18 to 75.
6. ECOG PS: 0~1.
7. Have not received any anti-tumor treatment for esophageal cancer in the past, including radiotherapy, chemotherapy, surgery, etc.
8. No contraindications to surgery.
9. Has sufficient organ function including (1) Blood routine: NE≥1.5×109/L; PLT≥100×109/L; HGB≥90 g/L (2)Comprehensive Metabolic Panel: bilirubin≤ 1.5×ULN; ALT≤2.5×ULN; AST≤2.5×ULN; sCr≤1.5×ULN or CrCl≥50 mL/min（Cocheroft-Gault) (3) Coagulation function: INR≤1.5; APTT≤1.5×ULN
10. Women of childbearing age must undergo a serological pregnancy test within 72 hrs before first administration. Women of childbearing age, or male subjects with childbearing age female partners, must take contraceptive measures from the first dose to three months after last administration.
11. Good compliance, willing to comply with follow-up schedules.

Exclusion Criteria:

1. Subjects have received or are receiving any of:

   1. anti-tumor interventions such as radiotherapy, chemotherapy, or other medications.
   2. immunosuppressants or systemic glucosteroids (prednisone equivalence> 10mg/d) within 2 weeks before the first administration, inhaled or topical use of glucosteroids (prednisone equivalence>10mg/d) is allowed if no known active autoimmune disease.
   3. live vaccine within 4 weeks before the first administration.
   4. major surgery or major injury within 4 weeks before the first administration.

2. Cancer-related exclusion criteria

   1. other cancers instead of ESCC
   2. unresectable or metastatic ESCC
   3. not comply with cⅡ-Ⅲ（cT2N1-2M0 or cT3N0-2M0, AJCC 8th）
   4. Subjects with other malignant tumors within 5 years before the first administration, but subjects with cervical carcinoma in situ, skin basal cell carcinoma, skin squamous cell carcinoma, localized prostate cancer received radical surgery and ductal carcinoma in situ that have received radical treatment and do not need other treatment can be included)

3. Other criteria

   1. Subjects have uncontrolled cardiovascular diseases, such as 1) heart failure ≥ NYHA class 2, 2) unstable angina 3) myocardial infarction within 1 year; 4) supraventricular or ventricular arrhythmia that needs treatment
   2. Subjects with any known active autoimmune disease
   3. Pregnant or breastfeeding female
   4. Presence of allergy or hypersensitivity to investigational medications
   5. HIV-positive or active hepatitis B (HBsAg positive and HBV-DNA ≥2000 IU/ml or ≥ 104 copies/mL) or active hepatitis C (HCV antibody positive) or active tuberculosis
   6. Investigators assessed there might be other factors that cause subjects to withdraw.

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: perioperative treatment with adebrelimab and CRT	Drug: Adebrelimab and nab-paclitaxel and carboplatin; Adebrelimab combined with nab-paclitaxel and carboplatin as neoadjuvant therapy; Radiation: Radiation; concurrent chemoradiotherapy; Procedure: standard oesophagectomy; standard oesophagectomy; Other: active surveillance; active surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year OS rate	An overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cCR rate	A clinical complete response rate (cCR) is defined as the complete disappearance of tumor lesions.	12 months
median EFS	An event-free survival (EFS) is defined as the duration from the start of treatment until disease recurrence or death from any cause, whichever occurs first.	24 months
median OS	An overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence.	24 months
Incidence, type and severity of adverse events as assessed by CTCAE 5.0	Including adverse events and complications. Incidence of adverse events using CTCAE 5.0; grade 3 adverse events and higher-grade will be reported.	24 months
quality of life (QOL)	Evaluate quality of life using EORTC QLQ-C30	24 months
quality of life (QOL) assessed by EORTC QLQ-OES18	Evaluate quality of life using EORTC QLQ-OES18	24 months

Collaborators and Investigators

• Sponsor: Zhigang Li

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 13, 2025
• Last Verified: March 1, 2025

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; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: MA-EC-II-017

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No