Spatial MSC Index for Predicting Anti-PD-1 Efficacy in Esophageal Cancer

NCT07745322 | Active Not Recruiting

• 1 other identifier: ESCC-MSC-2026
• Study Type: observational
• Target: 270
• Locations: 1 country
• Sites: 1

Brief Summary

The intratumoral microbiota is a key modulator of the tumor immune microenvironment. This study aims to clinically validate a novel, AI-driven digital pathology biomarker-the Microbial-Sensory Coupling (MSC) index-which measures the spatial proximity between the intratumoral bacterium Campylobacter gracilis(C. gracilis) and host Trace Amine-Associated Receptor 1 (TAAR1)+ tumor cells. The study will evaluate whether the MSC index, measured in pre-treatment tumor biopsy tissues, can accurately predict clinical responsiveness and survival outcomes in ESCC patients undergoing anti-PD-1-based immunotherapy.

Conditions

Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Percentage of patients achieving Complete Response (CR) or Partial Response (PR) based on RECIST 1.1 criteria, compared between MSC-high and MSC-low groups.

  Up to 12 months from the first dose of anti-PD-1 therapy

Secondary Outcomes (3)

• Diagnostic Accuracy (AUC)

  Up to 12 months from the first dose of anti-PD-1 therapy (best overall response assessment)

• Progression-Free Survival (PFS)

  Up to 24 months

• Overall Survival (OS)

  Up to 36 months

Study Arms (2)

Discovery Cohort (Model Development, Retrospective)

This retrospective cohort includes 120 ESCC patients who received anti-PD-1-based therapy. Archived pre-treatment FFPE biopsy specimens are retrieved and used to establish the MSC index mathematical model via multiplexed FISH and mIF combined with deep-learning image segmentation. ROC analysis is applied to determine the optimal diagnostic cut-off value for predicting anti-PD-1 responsiveness.

Validation Cohort (Independent, Retrospective)

This independent retrospective cohort includes 150 ESCC patients who received anti-PD-1-based therapy, identified from a non-overlapping case series. Archived pre-treatment FFPE biopsy specimens are used to validate the pre-determined MSC index cut-off value for its predictive specificity, sensitivity, and clinical utility in distinguishing immunotherapy responders from non-responders, as well as its association with PFS and OS.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with histologically confirmed esophageal squamous cell carcinoma (ESCC) who received standard anti-PD-1-based therapy (combined with chemotherapy or as monotherapy) at Beijing Cancer Hospital, retrospectively identified from institutional medical records and pathology archives. The study comprises two retrospective cohorts: a discovery cohort (n=120) used to construct the MSC index model, and an independent validation cohort (n=150) used to validate its predictive performance. Eligible cases are adults (aged 18 years and older) with ECOG performance status 0-1 at treatment initiation, at least one measurable lesion per RECIST 1.1 at baseline, adequate archived pre-treatment FFPE tumor tissue for dual ISH-IF spatial analysis, and complete follow-up data. Cases are included consecutively regardless of sex or ethnicity.

You may qualify if:

• Histologically confirmed esophageal squamous cell carcinoma (ESCC).
• Received standard anti-PD-1 antibody therapy (e.g., pembrolizumab, camrelizumab, sintilimab, toripalimab) combined with chemotherapy or as monotherapy, with at least one post-treatment response evaluation available.
• Availability of adequate, high-quality archived pre-treatment tumor tissue biopsies (FFPE blocks or unstained slides) containing sufficient tumor and stromal areas.
• At least one measurable target lesion according to RECIST 1.1 criteria at baseline.
• ECOG performance status of 0 or 1 at the initiation of anti-PD-1 therapy.
• Complete clinicopathological and follow-up data retrievable from medical records.

You may not qualify if:

• Histology other than squamous cell carcinoma (e.g., adenocarcinoma, small cell carcinoma).
• Prior systemic exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, or other immunotherapy agents.
• Concomitant systemic antibiotic, antifungal, or antiviral treatment within 14 days prior to tissue biopsy collection.
• Active autoimmune diseases or psychiatric disorders that prevent compliance.
• Insufficient tumor tissue specimen for dual ISH-IF spatial analysis.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Peking University Cancer Hospital & Institute

Beijing, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms

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

Study Officials

• Jie Chen

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2026
• First Posted: August 4, 2026
• Study Start: May 20, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 4, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)