Neoadjuvant Adebrelimab Plus Chemotherapy for Resectable ESCC: a Single Arm, Prospective Phase 2 Clinical Trial

The investigators will conduct a single-arm prospective study to evaluate the efficacy and safety of neoadjuvant therapy with adebrelimab (SHR-1316) and chemotherapy in patients with resectable esophageal squamous cell carcinoma (ESCC).

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Immunotherapy: Adebrelimab; Drug: chemotherapy: carboplatin plus nab-paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhigang Li, MD, PhD; Phone Number: 18960619260; Email: dr_lizhigang@163.com
• Study Contact Backup: Name: Yang Yang; Phone Number: 86 21-22200000*2116; Email: yangyang@shsmu.edu.cn

Study Locations

• China
  • Shanghai, China
    • Shanghai Chest Hospital

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 medictions.
   2. immunosuppresants 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. non-recetable 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 arrthymia 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 withdrawl.

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: adebrelimab and chemotherapy	Drug: Immunotherapy: Adebrelimab; Adebrelimab 1200mg Q3W; Drug: chemotherapy: carboplatin plus nab-paclitaxel; carboplatin plus nab-paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR rate	The primary endpoint is a pCR rate, which is defined as the absence of any remaining tumor cells in both the main tumor and the nearby lymph nodes (ypT0N0) as per the AJCC 8th Edition TRG scoring system.	12 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 as assessed by enhanced CT, endoscopic ultrasound, and endoscopic biopsy.	12 months
R0 resection rate	A R0 resection rate is defined as the rate of complete tumor removal with negative resection margin microscopically	12 months
MPR rate	A major pathological response rate (MPR) is defined as the proportion of residual living tumor cells in the post-surgery specimen within the tumor bed being less than or equal to 10%.	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.	12 months
median OS	An overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence.	12 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 treatment-related adverse events and higher-grade will be reported	From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose
Potential biomarkers such as ctDNA or PD-L1 expression	Potential biomarkers such as ctDNA or PD-L1 expression will be explored and analysed using blood or tissues prior and post-treatment.	12 months

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: November 18, 2023
• First Submitted That Met QC Criteria: December 11, 2023
• First Posted (Actual): December 20, 2023

Study Record Updates

• Last Update Posted (Actual): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: MA-EC-II-015

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