Biomarker Based Neoadjuvant Strategies for Locally Advanced Resectable ESCC (ESCC)

Biomarker Based Neoadjuvant Strategies for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma: an Exploratory Phase II Single-arm Clinical Study

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.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Serplulimab; Drug: Paclitaxel+Cisplatin (Neoadjuvant Chemotherapy); Drug: Paclitaxel+Cisplatin(Concurrent Chemoradiotherapy); Radiation: Radiotherapy

Detailed Description

Esophageal cancer is a malignant tumor with a high incidence in China, with most patients diagnosed at the advanced stage. Traditional treatment modalities include surgery, chemoradiotherapy, and chemotherapy. However, under current standard treatments, approximately 50% of patients remain incurable, primarily due to postoperative recurrence and distant metastasis. Therefore, seeking a new treatment strategy to improve efficacy is crucial.

This clinical trial aims to evaluate the use of immune checkpoint inhibitors in neoadjuvant therapy based on CPS scoring to enhance the pathologic complete response (pCR) rate. Patients pathologically confirmed with esophageal squamous cell carcinoma (ESCC) will undergo surgical assessment for operability. Eligible patients will further undergo CPS testing and will receive different neoadjuvant treatment strategies based on CPS results: patients with CPS ≥20 will receive neoadjuvant immunotherapy alone; CPS 10-20 patients will receive neoadjuvant chemotherapy followed by immunotherapy; and CPS <10 patients will receive standard neoadjuvant chemoradiotherapy.

After completing neoadjuvant therapy, patients will rest for 4-6 weeks before undergoing curative surgery, which will be reassessed by thoracic surgeons for R0 resection feasibility preoperatively. Postoperatively, pathological evaluation will assess the pCR rate and other secondary study endpoints, with the most severe toxicities included in the analysis.

This study anticipates a group-wide pCR rate of 45% based on a PD-L1 biomarker-guided neoadjuvant treatment strategy. The trial is designed to exclude a pCR rate of 30% or lower using a one-sided 95% confidence interval (α set at 0.025) and 80% statistical power, with a total sample size of 90. The null hypothesis will be rejected if fewer than 34 patients achieve pCR in the entire cohort.

Based on reference studies (EC-CRT-001, ESCORT-1, JUPITER-06, and KEYNOTE-590) and CPS distribution data for esophageal squamous cell carcinoma from our institution, it is expected that the proportions of patients with CPS ≥20, 10-20, and <10 will be 10%, 40%, and 50%, respectively, corresponding to 9, 36, and 45 eligible patients for each group. It is anticipated that biological specimens will be obtained from more than 30 patients.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhao-han Lin; Phone Number: 0086-0591-86218329; Email: xhyyllwyh@163.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital
      • Contact: Zhao-han Lin; Phone Number: 0086-0591-86218329; Email: xhyyllwyh@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosis: Histologically confirmed esophageal squamous cell carcinoma (ESCC).
2. Stage: Resectable locally advanced ESCC (clinical stage II-III according to the AJCC/UICC 8th edition).
3. Age: 18-75 years old.
4. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
5. PD-L1 Expression: Available PD-L1 expression level (CPS).
6. Surgical Eligibility: Assessed as eligible for surgical resection by a thoracic surgeon.

7. 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.
8. Informed Consent: Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

1. Distant Metastasis: Presence of distant metastasis.
2. 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.
3. Autoimmune Diseases: History of active autoimmune diseases requiring systemic treatment within the past 2 years.
4. Infections: Active infection requiring systemic therapy.
5. 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.
6. Previous Treatment: Previous treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies.
7. Pregnancy and Lactation: Pregnant or breastfeeding women. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization.
8. Allergies: Known allergy or hypersensitivity to study drugs or any excipient of these medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High PD-L1 Expression Group (CPS ≥ 20); Patients with high PD-L1 expression (CPS ≥ 20) will receive neoadjuvant immunotherapy alone. This treatment consists of serplulimab for 2 cycles.	Drug: Serplulimab; Serplulimab (300 mg) administered intravenously on day 1 of each 21-day cycle for 2 cycles.
Experimental: Moderate PD-L1 Expression Group (CPS 10-20); 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; Serplulimab (300 mg) administered intravenously on day 1 of each 21-day cycle for 2 cycles.; Drug: Paclitaxel+Cisplatin (Neoadjuvant Chemotherapy); 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.
Experimental: Low PD-L1 Expression Group (CPS < 10); 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); 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.; Radiation: Radiotherapy; Radiotherapy at a dose of 40 Gy, delivered in 20 fractions over 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 Resection Rate	The proportion of patients achieving an R0 resection, defined as a microscopically margin-negative resection with no residual tumor at the resection margins.	after the pathological examination of surgical speciments ie within 14 days after the operation
Treatment-Related Toxicity	The incidence and severity of treatment-related adverse events, graded according to CTCAE 5.0. This includes adverse events related to Serplulimab, Paclitaxel, Cisplatin, and radiotherapy, as well as surgical complications.	From the start of treatment to 30 days post-surgery
3-Year Disease-Free Survival (DFS)	The percentage of patients who remain disease-free three years after surgical resection. DFS is defined as the time from R0 resection to the first occurrence of disease recurrence or death from any cause.	36 months after treatment completion
Tumor Mutational Burden (TMB)	Tumor mutational burden (TMB) score as measured in tumor tissue samples.	36 months after treatment completion.
Microsatellite Instability (MSI)	Percentage of patients with high microsatellite instability (MSI-H) in tumor tissue	36 months after treatment completion
Circulating Tumor DNA (ctDNA)	Change in circulating tumor DNA (ctDNA) levels as measured by liquid biopsy.	36 months after treatment completion
major pathological response	tumor regression ≥90%	Patients were evaluated 2 to 4 weeks postoperatively.

Collaborators and Investigators

• Sponsor: Fujian Medical University Union Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: September 13, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; Biomarkers; Neoadjuvant Therapy; Esophageal Cancer; Chemoradiotherapy; Pathological Complete Response (pCR)
• 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; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Therapeutics; Combined Modality Therapy; Radiotherapy; Neoadjuvant Therapy; TP protocol
• Other Study ID Numbers: BIONS-R

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
• product manufactured in and exported from the U.S.: No