Immune Indicator Model for Predicting Efficacy of PD-1 Monoclonal Antibody

Construction and Application of Immune Indicator Model for Predicting Efficacy of PD-1 Monoclonal Antibody in the Treatment of Advanced Esophageal Cancer

200 patients with advanced esophageal cancer who received PD-1 monoclonal antibody treatment would be enrolled in this study. Changes in peripheral blood immune cells before and after treatment would be recorded and used for machine learning to establish a prediction model for the efficacy of PD-1 monoclonal antibody treatment.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma; PD-1 Inhibitor

Detailed Description

PD-1 monoclonal antibody has been used as a first-line drug for the treatment of advanced esophageal cancer, however, the ideal predictor of efficacy has not been established. The peripheral immune system plays an important role in driving anti-tumor effects, and the characteristics of peripheral immune cells can predict the effect of PD-1 monoclonal antibody therapy. However, the value of a single indicator for predicting the effect of PD-1 monoclonal antibody therapy is greatly limited. 200 patients with advanced esophageal cancer who received PD-1 monoclonal antibody treatment would be enrolled. Changes in peripheral blood immune cells before and after treatment would be recorded and used for machine learning to establish a prediction model for the efficacy of PD-1 monoclonal antibody treatment. The application between the indicator model and the expression level of PD-L1 in tumor tissue in predicting the efficacy of PD-1 monoclonal antibody in advanced esophageal cancer will be also study. This study aims to establish a peripheral blood immune cell-based models to predict the efficacy of PD-1 monoclonal antibody therapy for advanced esophageal cancer, provide a basis for guiding the selection of treatment options for advanced esophageal cancer, and improve the efficacy of PD-1 monoclonal antibody therapy.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • Nanfang Hospital
    • Contact: Lei Zheng

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with advanced esophageal cell carcinoma who are ready to receive PD-1 monoclonal antibody therpy

Description

Inclusion Criteria:

• Patients with metastatic advanced esophageal squamous cell carcinoma (stage IV) confirmed by histology or cytology who are ready to receive PD-1 monoclonal antibody combined with TP chemotherapy regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status score between 0 and 2.
• Have measurable lesions.
• Expected survival > 3 months.
• Subjects who have received anti-tumor therapy in the past should be enrolled after the toxicity of the previous treatment has returned to the baseline level (except for residual hair loss effects) or CTCAE v4.03 scale score ≤ 1.
• Female or male subjects of reproductive age and their partners should agree to use effective contraception from the time of signing the ICF until 6 months after the last dose of study drug.
• Absolute neutrophil count (ANC) ≥1.5×109/L, platelets ≥100×109/L, hemoglobin ≥9 g/dL. Liver: Bilirubin ≤1.5 times the upper limit of normal, alkaline phosphatase (AP) , Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 times the upper limit of normal (AP, AST, ALT ≤5 times the upper limit of normal are allowed if there is liver metastases) Renal: Calculated creatinine clearance ≥45 mL/min.

Exclusion Criteria:

• Have active, or have had an autoimmune disease that is likely to recur (eg, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, vasculitis, psoriasis, etc.) or at risk (e.g., organ transplant recipients requiring immunosuppressive therapy).
• Subjects who need to receive glucocorticoid (prednisone > 10 mg/day or equivalent dose of other similar drugs) or other immunosuppressive therapy due to certain conditions within 14 days prior to study drug administration.
• Major surgery, or radical radiation therapy, or palliative radiation therapy within the previous 14 days, or radiopharmaceuticals (strontium, samarium, etc.) within 56 days before starting study treatment.
• Received systemic anti-tumor therapy, including immunotherapy, biological therapy (tumor vaccines, cytokines, or growth factors to control cancer), etc. 14 days before starting study treatment.
• Have suffered from interstitial lung disease, chemical pneumonia, hypersensitivity pneumonitis, connective tissue disease pneumonia, pulmonary fibrosis, acute lung disease, etc. (except for local interstitial pneumonia induced by radiotherapy), or uncontrolled systemic disease, including diabetes and hypertension.
• Patients with human immunodeficiency virus (HIV) infection.
• patients with active pulmonary tuberculosis.
• Any active infection requiring systemic therapy by intravenous infusion within 2 weeks prior to the first dose of study drug.
• People who have received a solid organ transplant.
• Patients who have received any antibody/drug (including anti-programmed death-1 (PD-1), PD-L1, etc.) targeting T-cell co-regulatory proteins (immune checkpoints).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
reactive group; According to the treatment effect, the patients were divided into two groups: reactive and non-reactive.
non-reactive group; According to the treatment effect, the patients were divided into two groups: reactive and non-reactive.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
peripheral blood immune cells and immune molecules	Including absolute count of lymphocyte subsets, T lymphocyte subsets, B lymphocyte subsets, NK cell subsets, regulatory T cells, MDSC, etc. and IL-6, IL-10, etc.	2022.1-2026.12
Imaging examination	Including X-rays, CT, PET-CT and MR	2022.1-2026.12

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Investigators: Study Director: Lei Zheng, Nanfang Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2022
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: July 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma
• Other Study ID Numbers: NFEC-2022-079

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