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

Phase 2

Not yet recruiting

• Conditions: Esophageal Squamous Cell Carcinoma

• Registration Number: NCT06178211
• Lead Sponsor: Shanghai Chest Hospital

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-18
• Status Verified: 2023-12
• Study Start: 2023-12
• Study First Submitted QC: 2023-12-11
• Last Update Submitted: 2023-12-11
• Study First Posted: 2023-12-20
• Last Update Posted: 2023-12-20
• Primary Completion: 2025-03
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 36

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
pCR rate	12 months	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.

Secondary Outcome Measures

Name	Time	Method
cCR rate	12 months	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.
R0 resection rate	12 months	A R0 resection rate is defined as the rate of complete tumor removal with negative resection margin microscopically
MPR rate	12 months	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%.
median EFS	12 months	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.
median OS	12 months	An overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence.
Incidence, type and severity of adverse events as assessed by CTCAE 5.0	From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose	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
Potential biomarkers such as ctDNA or PD-L1 expression	12 months	Potential biomarkers such as ctDNA or PD-L1 expression will be explored and analysed using blood or tissues prior and post-treatment.

Trial Locations

Locations (1)

Shanghai Chest Hospital; 🇨🇳 Shanghai, China