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NCT Number: NCT07745322

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Peking University Cancer Hospital & Institute

Beijing, China

About this study

Emerging evidence indicates that C. gracilis secretes a unique xenometabolite, cadaverine, which binds to and activates the host TAAR1 receptor on ESCC cells, thereby promoting tyrosine kinase FAK-dependent secretion of the chemokine and cytokine. This pathway orchestrates immune cells, leading to resistance to anti-PD-1 therapy.

This retrospective observational study employs multiplexed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) / multiplex immunofluorescence (mIF), combined with deep-learning-based image segmentation, to quantify the spatial relationship between C. gracilis and TAAR1+ tumor cells.

The study consists of two phases:

  • Discovery Phase (Cohort A, n=120): To establish the mathematical model of the MSC index and determine the optimal cut-off value using ROC analysis.
  • Validation Phase (Cohort B, n=150): An independent retrospective cohort to validate the predictive specificity, sensitivity, and clinical utility (PFS, OS, and ORR) of the pre-determined MSC index cut-off.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Primary outcomes

  1. Objective Response Rate (ORR)

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

    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.

Secondary outcomes

  1. Diagnostic Accuracy (AUC)

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

    Calculated using ROC analysis to evaluate the capability of the MSC index to discriminate between immunotherapy responders (CR/PR) and non-responders (SD/PD).

  2. Progression-Free Survival (PFS)

    Time frame: Up to 24 months

    Time from the first dose of anti-PD-1 therapy to the date of objective disease progression or death from any cause, whichever occurs first.

  3. Overall Survival (OS)

    Time frame: Up to 36 months

    Time from the first dose of anti-PD-1 therapy to the date of death from any cause.

Sponsors and collaborators

Lead sponsor

Peking University Cancer Hospital & Institute

Other

Registry information

Official study title

Clinical Validation of the Microbial-Sensory Coupling (MSC) Index as a Predictive Biomarker for Anti-PD-1 Immunotherapy Responsiveness in Esophageal Squamous Cell Carcinoma Patients

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Aug 4, 2026
Registry last updated
Aug 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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