Adebrelimab Plus Apatinib and Etoposide for the Treatment of HER2-Negative Breast Cancer Brain Metastasis

Last updated: December 5, 2024
Sponsor: Beijing 302 Hospital
Overall Status: Active - Recruiting

Phase

2

Condition

Neoplasm Metastasis

Treatment

Adebrelimab

Etoposide

Apatinib

Clinical Study ID

NCT06418594
MA-BC-II-070
  • Ages > 18
  • Female

Study Summary

Some studies have shown that approximately 15% of patients with advanced hormone receptor (HR) positive breast cancer and 1/3 of triple negative breast cancer will develop brain metastasis. At present, there is no unified drug treatment standard for HER2-negative breast cancer brain metastasis (BCBM). The evidence of single traditional chemotherapy drug as the main treatment of brain metastasis is not sufficient. Some exploratory studies on HER2-negative BCBM have shown that the central nervous system objective response rate (CNS-ORR) of anti-angiogenic drugs combined with chemotherapy is around 55%-80%。 Adebrelimab (a humanized PD-L1 monoclonal antibody) specifically blocks the binding of PD-1 and PD-L1, terminates the immunosuppressive signal produced by T cells, and makes T cells re-recognize tumor cells and kill them, thereby inhibiting tumor growth. In China, Adebelizumab has been approved for using in combination with chemotherapy as a first-line treatment for extensive stage small cell lung cancer. Apatinib (a small molecule VEGFR tyrosine kinase inhibitor) mainly plays an anti-angiogenic effect in the treatment of malignant tumors by inhibiting VEGFR. Apatinib has been approved monotherapy for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma that has progressed or relapsed after at least two systematic chemotherapies, advanced liver cancer that has failed or is intolerable after at least first-line systematic treatment, and first-line treatment in patients with unresectable or metastatic hepatocellular carcinoma combined with camrelizumab.

Due to the lack of effective drug therapy for HER2-negative BCBM, a variety of treatment combinations are still being explored. We hypothesized that adebrelimab plus apatinib and etoposide is an explorable and effective treatment for HER2- negative BCBM.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Female, aged ≥18 years

  • Expected survival time ≥3 months.

  • Histologically or cytologically confirmed HER2-negative (IHC 0 or 1+; or IHC 2+ ISHnegative) locally recurrent or metastatic disease

  • New brain metastasis or brain metastasis progression after treatment

  • HR+ advanced breast cancer with prior CDK4/6 inhibitor treatment failure or theinvestigator deems unsuitable for CDK4/6 inhibitors

  • At least one intracranial measurable lesion as defined by RECIST V1.1 criteria；

  • ECOG PS 0-2；

  • Patients must have the ability to swallow oral medication；

  • Prior WBRT, stereotactic radiosurgery, and surgical resection are allowed；

  • Organ function levels are basically normal, and the investigator believes that thestudy drug can be applied：

  • Voluntarily join this study, sign the informed consent, have good compliance, andare willing to cooperate with follow-up

Exclusion

Exclusion Criteria:

  • Urgent need for local treatment of brain metastasis

  • Immunohistochemistry HER2 positive (IHC 3 or IHC 2 ISH amplification)

  • Previously treated with Apatinib, Avelumab, or VP-16；

  • Severe dysfunction of important organs such as the heart, liver, or kidneys；

  • Inability to swallow, chronic diarrhea, and intestinal obstruction, with multiplefactors affecting drug administration and absorption；

  • Participants diagnosed with any other malignant tumor within 5 years before thisstudy, excluding non-melanoma skin cancer that has undergone radical treatment.Basal cell or squamous cell skin cancer or cervical carcinoma in situ and thyroidpapillary carcinoma。

  • Patients who allergy to any component of the drugs in this protocol; patients withhistory of immunodeficiency, including HIV positive, HCV, active hepatitis B, orother acquired or congenital immunodeficiency diseases, or history of organtransplantation

  • History of any cardiac disease, including: (1) arrhythmia requiring medication orclinically significant; (2) myocardial infarction; (3) heart failure; (4) any othercardiac disease judged by the investigator to be unsuitable for participation inthis trial, etc.

  • Pregnant or lactation female patients; females of childbearing age with a positivebaseline pregnancy test or unwilling to take effective contraceptive measures duringthe entire trial period；

  • According to the investigator's judgment, there are severe accompanying diseasesthat endanger the patient's safety or affect the completion of the study (includingbut not limited to uncontrolled severe hypertension, severe diabetes, activeinfection, etc.).

Study Design

Total Participants: 30
Treatment Group(s): 3
Primary Treatment: Adebrelimab
Phase: 2
Study Start date:
October 10, 2024
Estimated Completion Date:
December 31, 2026

Connect with a study center

  • The Fifth Medical Center of PLA General Hospital

    Beijing, Beijing 100071
    China

    Active - Recruiting

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