Esophageal Squamous Cell CarcinomaNCT07745322
Spatial MSC Index for Predicting Anti-PD-1 Efficacy in Esophageal Cancer
An observational study of Esophageal Squamous Cell Carcinoma and Esophageal Neoplasms, run by Peking University Cancer Hospital & Institute at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms
- How many people
- 270 participants
- Where
- 1 siteChina
- Study dates
- 20 May 2026to 31 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
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.
Read the detailed description
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.
- Medical subject headings
- Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 12 months from the first dose of anti-PD-1 therapy
Secondary outcomes (3)
Diagnostic Accuracy (AUC)
Calculated using ROC analysis to evaluate the capability of the MSC index to discriminate between immunotherapy responders (CR/PR) and non-responders (SD/PD).
Measured: Up to 12 months from the first dose of anti-PD-1 therapy (best overall response assessment)
Progression-Free Survival (PFS)
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.
Measured: Up to 24 months
Overall Survival (OS)
Time from the first dose of anti-PD-1 therapy to the date of death from any cause.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2026
- Study start20 May 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Peking University Cancer Hospital & InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 270 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Cancer Hospital & Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jie Chen, Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07745322
- Sponsor's protocol ID
- ESCC-MSC-2026
- Status last verified
- Jul 2026
- First submitted
- 30 Jul 2026
- Last updated
- 4 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT07745322
- Acronym / sponsor ID
- ESCC-MSC-2026
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- Peking University Cancer Hospital & InstituteUniversity, hospital or other
- Study start
- 20 May 2026 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 4 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
3 secondary outcomes
Diagnostic Accuracy (AUC)
Time frame: Up to 12 months from the first dose of anti-PD-1 therapy (best overall response assessment)
Progression-Free Survival (PFS)
Time frame: Up to 24 months
Overall Survival (OS)
Time frame: Up to 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jie Chen principal investigator
Peking University Cancer Hospital & Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Esophageal Squamous Cell Carcinoma and Esophageal Neoplasms, run by Peking University Cancer Hospital & Institute at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Up to 12 months from the first dose of anti-PD-1 therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2026.