Observational Study on the Sensitivity of Neoadjuvant Immunotherapy in Early Triple-Negative Breast Cancer

NCT06448169 | Not Yet Recruiting

• 1 other identifier: STNBC001
• Study Type: observational
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

Studies have reported that tumors with the same immunogenic mutations may induce T cell receptor (TCR) domains with similar antigen recognition functions. By assembling the complementarity-determining region 3 (CDR3) of TCRs from RNA-seq data and correlating them with 9142 samples from TCGA data, an in-depth analysis of the TCR pool in the tumor microenvironment found a strong correlation between the CDR3 sequences of tumor-infiltrating T cells and tumor mutation burden. Fairfax et al. found that in patients responding to tumor immunotherapy, the TCR immune pool of CD8+ T cells produces many clones with extremely high abundance (exceeding 0.5%) . Cader et al. also found significant changes in the TCR immune pool of patients with Hodgkin's lymphoma responding to PD-1 tumor immunotherapy. Based on these theoretical foundations, evaluating the dynamic changes of the TCR immune pool is expected to be used to analyze the immune characteristics and changes in diseases such as malignant tumors.

Conditions

Triple Negative Breast Cancer; Neoadjuvant Immunotherapy; Sensitivity

Keywords

Sensitivity; Neoadjuvant Immunotherapy; Triple-Negative Breast Cancer; Dynamic Immune Signature Analysis

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate

  patients with pCR/all patients \*100%

  after operation, an average of 5 months

Secondary Outcomes (3)

• clinical response rate

  before operation,an average of 5 months

• immune-related adverse events

  during treatment, ,an average of 5 months

• drug resistance

  during treatment,,an average of 5 months

Interventions

PD-1 inhibitor DRUG

PD-1 inhibitor combined with neoadjuvant chemotherapy

Also known as: Tislelizumab

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

early stage triple negative breast cancer patients

You may qualify if:

• Age: 18-60 years old;
• Histologically confirmed triple-negative breast cancer, with immunohistochemistry showing ER \<1%, PR \<1%, HER2-negative (IHC 0 or 1+; or IHC 2+ ISH-negative);
• Imaging-confirmed non-metastatic disease;
• Clinical efficacy can be evaluated according to RECIST criteria;
• European Functional Handicap Scale (MRC) of 0-2;
• The investigator determines that the treatment is tolerable based on the patient's organ function level;
• Volunteers willing to participate in this study, sign the informed consent, have good compliance, and are willing to cooperate with follow-up.

You may not qualify if:

• Immunohistochemistry showing HER2-positive (IHC 3 or IHC 2 ISH-amplified);
• Previously treated;
• Severe dysfunction of important organs such as heart, liver, and kidneys;
• Patients with diseases unsuitable for immunotherapy;
• Known allergy history to any component of the drugs in this regimen;
• History of immune deficiency, including HIV-positive, HCV, active hepatitis B, or other acquired or congenital immune deficiency diseases, or a history of organ transplantation;
• Any cardiac disease, including: ① Medically treated or clinically significant arrhythmias; ② Myocardial infarction; ③ Heart failure; ④ Any other cardiac disease judged by the investigator as unsuitable for participation in this trial;
• Pregnant or lactating women, fertile women with positive baseline pregnancy test or those unwilling to take effective contraceptive measures during the entire trial;
• According to the investigator's judgment, there are accompanying diseases that seriously endanger the safety of the patient or affect the completion of the study (including but not limited to severe hypertension uncontrollable by drugs, severe diabetes, active infections, etc.);
• Long-term use of drugs that affect the components of peripheral blood immune cells, such as recombinant human erythropoietin, recombinant human granulocyte colony-stimulating factor, recombinant human interleukin, or Likejun tablets;
• Received immunosuppressive therapy within 2 weeks;
• Hematological precancerous diseases, such as myelodysplastic syndrome, and coagulation disorders.

Sponsors & Collaborators

• Shandong University: lead
• Chinese PLA General Hospital: collaborator

Biospecimen

Retention: SAMPLES WITHOUT DNA

Utilize deep sequencing technology to capture the molecular characteristics of the TCR immunome pool in the peripheral blood of patients with triple-negative breast cancer at different time points before and after neoadjuvant therapy.

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Hypersensitivity

Interventions

Immune Checkpoint Inhibitors; tislelizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: May 12, 2024
• First Posted: June 7, 2024
• Study Start: May 30, 2024
• Primary Completion: February 28, 2026
• Study Completion: April 30, 2026
• Last Updated: June 7, 2024

Record last verified: 2024-05