Predictive Biomarkers for PD-1 Inhibitor Response in Squamous Cell Carcinoma

NCT07147361 | Active Not Recruiting

• 1 other identifier: NCC5443
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter retrospective-prospective cohort study evaluates predictive biomarker and tissue-pathology features for response to PD-1 inhibitor-based therapy in patients with squamous cell carcinoma (SCC). Model inputs include blood ELISA, tissue multiplex immunofluorescence (mIF), PD-L1 assessment, pretreatment biopsy/H\&E-based pathology features, and baseline clinicopathological variables, assessed individually or in combination. The retrospective component will analyze clinical data and pretreatment tissue and blood specimens from SCC patients treated with PD-1 inhibitor-based therapy from May 2020 onward across participating centers. These data will be used to develop and refine a predictive model or risk-score framework and to evaluate associations with objective response rate (ORR), pathological response where applicable, duration of response (DoR), progression-free survival (PFS), event-free survival (EFS), and overall survival (OS). The prospective component begins in September 2025 and will enroll up to 800 participants. Eligible patients may receive PD-1 inhibitor therapy with or without chemotherapy, including disease-specific cohorts receiving neoadjuvant anti-PD-1 therapy plus chemotherapy where applicable. Baseline clinical data and pretreatment samples will be collected before treatment initiation. Tumor tissue, biopsy or H\&E slides obtained within 6 months where available, and blood samples collected within 28 days where available will be used for biomarker and tissue-pathology analyses. Patients will be followed at baseline and at weeks 4, 8, and 12 where applicable, with quarterly survival follow-up. Response may be assessed using RECIST 1.1 and/or pathological response criteria, including tumor regression grade where applicable; for neoadjuvant patients, postoperative tumor regression grade and treatment failure before surgery may be incorporated according to a prespecified response-assessment rule. Within the prospective component, the ESCC-specific cohort includes consecutive treatment-naive patients receiving neoadjuvant anti-PD-1 blockade plus chemotherapy and supports locked-model evaluation using pretreatment endoscopic biopsy H\&E slides.

Conditions

Esophageal Squamous Cell Carcinoma (ESCC); Cervical Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Head and Neck Squamous Carcinoma

Outcome Measures

Primary Outcomes (1)

• Area under ROC curve

  The primary outcome is the area under the receiver operating characteristic curve (AUC) of the predictive model or risk-score framework for classifying patient-level treatment response to PD-1 inhibitor-based therapy. Treatment response may be assessed using RECIST 1.1 and/or pathological response criteria, including tumor regression grade where applicable.

  From enrollment to protocol-defined response assessment, up to 6 months.

Secondary Outcomes (2)

• Event-free survival

  From enrollment to first event or last follow-up, up to 5 years.

• Overall survival

  From enrollment to death or last follow-up, up to 5 years.

Study Arms (2)

Retrospective SCC Cohort

Patients with pathologically confirmed esophageal, head and neck, cervical, or lung squamous cell carcinoma who received PD-1 inhibitor-based therapy, with or without chemotherapy, at participating centers from May 2020 onward. Existing baseline clinical data and available pretreatment tumor biopsy tissue, H\&E slides, and blood specimens are retrospectively collected for development and refinement of biomarker- and tissue-based prediction models and for evaluation of associations with treatment response and time-to-event outcomes. Treatment was selected as part of routine clinical care and was not assigned by this observational study.

Prospective SCC Cohort

Adults with pathologically confirmed esophageal, head and neck, cervical, or lung squamous cell carcinoma are prospectively enrolled from September 2025 before planned PD-1 inhibitor-based therapy, with or without chemotherapy. Within this prospective component, the ESCC-specific cohort includes consecutive treatment-naive patients receiving neoadjuvant anti-PD-1 blockade plus chemotherapy at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Pretreatment clinical data and available tumor tissue, H\&E slides, and blood samples are collected, and participants are followed for treatment response and survival outcomes. Treatment is selected as part of routine clinical care and is not assigned by this observational study.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study enrolls patients with confirmed squamous cell carcinoma (SCC), including esophageal, head/neck, cervical, and lung subtypes, regardless of resectability. Participants must be scheduled for neoadjuvant or first-line PD-1 inhibitor therapy and provide pretreatment tumor and blood samples. Key inclusion requires capacity for informed consent; concurrent malignancies or prior anticancer treatments are exclusions. All subjects must provide written informed consent and undergo baseline assessments: clinical data collection, archival/fresh tumor tissue acquisition (within 6 months), and peripheral blood sampling (within 28 days) for biomarker analysis.

You may qualify if:

• Patients with pathologically confirmed esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), cervical squamous cell carcinoma (CSCC), or lung squamous cell carcinoma (LSCC), regardless of surgical eligibility
• For surgically eligible patients: Planned to receive neoadjuvant PD-1 inhibitor ± chemotherapy as first-line treatment
• For surgically ineligible patients: Planned to receive PD-1 inhibitor ± chemotherapy as first-line treatment
• Availability of pre-treatment biopsy tissue and baseline blood samples
• Capable of providing informed consent

You may not qualify if:

• Patients with concurrent other types of malignancies
• Patients who have already undergone prior antitumor therapy

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Department of Etiology and Carcinogenesis

Beijing, Beijing Municipality, 100021, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

① Tissue samples: To collect residual pre-treatment biopsy tissue samples from enrolled individuals, which are left over from routine clinical diagnosis and treatment. ② Blood samples: To collect residual blood samples from enrolled individuals, which are left over from routine clinical diagnosis and treatment.

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Department of Etiology and Carcinogenesis

  Cancer Hospital Chinese Academy of Medical Scienc

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study Record Dates

• First Submitted: August 14, 2025
• First Posted: August 29, 2025
• Study Start: May 28, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: July 13, 2026

Record last verified: 2026-07

Locations

CN (1)