Biomarker Based Neoadjuvant Strategies for Locally Advanced Resectable ESCC

NCT06601309 | Recruiting Phase 2 DMC

• 1 other identifier: BIONS-R
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the impact of the neoadjuvant treatment strategy based on CPS score on the pathological complete response (pCR) rate in patients with resectable locally advanced esophageal cancer.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Esophageal Cancer; Neoadjuvant Therapy; Pathological Complete Response (pCR); Immunotherapy; Chemoradiotherapy; Biomarkers

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  The proportion of patients achieving a pathological complete response (pCR) after neoadjuvant treatment and surgical resection. pCR is defined as the absence of any residual invasive cancer in the resected esophagus and all sampled lymph nodes (ypT0N0) based on hematoxylin and eosin staining.

  after the pathological examination of surgical speciments within 14 days after the operation

Secondary Outcomes (7)

• R0 Resection Rate

  after the pathological examination of surgical speciments ie within 14 days after the operation

• Treatment-Related Toxicity

  From the start of treatment to 30 days post-surgery

• 3-Year Disease-Free Survival (DFS)

  36 months after treatment completion

• Tumor Mutational Burden (TMB)

  36 months after treatment completion.

• Microsatellite Instability (MSI)

  36 months after treatment completion

Study Arms (3)

High PD-L1 Expression Group (CPS ≥ 20)

EXPERIMENTAL

Patients with high PD-L1 expression (CPS ≥ 20) will receive neoadjuvant immunotherapy alone. This treatment consists of serplulimab for 2 cycles.

Drug: Serplulimab

Moderate PD-L1 Expression Group (CPS 10-20)

EXPERIMENTAL

Patients with moderate PD-L1 expression (CPS 10-20) will receive neoadjuvant chemotherapy combined with immunotherapy. This includes paclitaxel and cisplatin along with serplulimab for 2 cycles.

Drug: Serplulimab; Drug: Paclitaxel+Cisplatin (Neoadjuvant Chemotherapy)

Low PD-L1 Expression Group (CPS < 10)

EXPERIMENTAL

Patients with low PD-L1 expression (CPS \< 10) will receive standard neoadjuvant chemoradiotherapy. This includes paclitaxel and cisplatin along with radiotherapy (40 Gy in 20 fractions over 4 weeks).

Drug: Paclitaxel+Cisplatin(Concurrent Chemoradiotherapy); Radiation: Radiotherapy

Interventions

Serplulimab DRUG

Serplulimab (300 mg) administered intravenously on day 1 of each 21-day cycle for 2 cycles.

High PD-L1 Expression Group (CPS ≥ 20); Moderate PD-L1 Expression Group (CPS 10-20)

Paclitaxel+Cisplatin (Neoadjuvant Chemotherapy) DRUG

Paclitaxel (175 mg/m²) and Cisplatin (75 mg/m²) administered intravenously on day 1 of each 21-day cycle for 2 cycles as part of neoadjuvant chemotherapy.

Moderate PD-L1 Expression Group (CPS 10-20)

Paclitaxel+Cisplatin(Concurrent Chemoradiotherapy) DRUG

Paclitaxel (50 mg/m²) and Cisplatin (25 mg/m²) administered intravenously on days 1, 8, 15, and 22 of a 4-week cycle as part of concurrent chemoradiotherapy.

Low PD-L1 Expression Group (CPS < 10)

Radiotherapy RADIATION

Radiotherapy at a dose of 40 Gy, delivered in 20 fractions over 4 weeks.

Low PD-L1 Expression Group (CPS < 10)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis: Histologically confirmed esophageal squamous cell carcinoma (ESCC).
• Stage: Resectable locally advanced ESCC (clinical stage II-III according to the AJCC/UICC 8th edition).
• Age: 18-75 years old.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• PD-L1 Expression: Available PD-L1 expression level (CPS).
• Surgical Eligibility: Assessed as eligible for surgical resection by a thoracic surgeon.
• Laboratory Requirements:
• Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, Platelets ≥ 100 x 10\^9/L, Hemoglobin ≥ 9 g/dL.
• Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), AST and ALT ≤ 2.5 x ULN.
• Adequate renal function: Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min.
• Informed Consent: Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Distant Metastasis: Presence of distant metastasis.
• Other Malignancies: History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin carcinoma, or other localized non-invasive malignancy.
• Autoimmune Diseases: History of active autoimmune diseases requiring systemic treatment within the past 2 years.
• Infections: Active infection requiring systemic therapy.
• Uncontrolled Conditions: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Previous Treatment: Previous treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies.
• Pregnancy and Lactation: Pregnant or breastfeeding women. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization.
• Allergies: Known allergy or hypersensitivity to study drugs or any excipient of these medications.

Sponsors & Collaborators

• Fujian Medical University Union Hospital: lead

Study Sites (1)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms

Interventions

TP protocol; Neoadjuvant Therapy; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Central Study Contacts

Zhao-han Lin

CONTACT

0086-0591-86218329; xhyyllwyh@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This parallel assignment interventional study evaluates the efficacy and safety of biomarker-based neoadjuvant treatments in resectable locally advanced esophageal squamous cell carcinoma (ESCC). Patients are stratified by PD-L1 expression (CPS) into three groups: 1. High PD-L1 Expression (CPS ≥ 20) Neoadjuvant immunotherapy alone. 2. Moderate PD-L1 Expression (CPS 10-20): Neoadjuvant chemotherapy combined with immunotherapy. 3. Low PD-L1 Expression (CPS \< 10): Standard neoadjuvant chemoradiotherapy. All treatments are followed by surgical resection. The primary endpoint is the pathological complete response (pCR) rate post-surgery. Secondary endpoints include treatment-related toxicity, R0 resection rate, and 3-year disease-free survival (DFS). Exploratory endpoints include identifying molecular biomarkers linked to treatment efficacy.

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: July 11, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)