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

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

NCT ID: NCT06418594

Condition: HER2-negative Breast Cancer Brain Metastases

Conditions: Official terms:
Breast Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Etoposide
Apatinib

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: This study adopts a single-arm, open-label design, planning to enroll 30 patients with HER2-negative breast cancer brain metastasis.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Adebrelimab
Description: Adebrelimab: 1200mg, ivgtt, administered on the first day of each cycle, with a cycle of 21 days
Arm group label: Adebrelimab+Apatinib+Etoposide

Intervention type: Drug
Intervention name: Apatinib
Description: Apatinib: 250 mg, oral, once daily, continuous use, with a cycle of 21 days
Arm group label: Adebrelimab+Apatinib+Etoposide

Other name: Apatinib Mesylate Tablets

Intervention type: Drug
Intervention name: Etoposide
Description: Etoposide: 50mg/day, oral, administered on days 1-14 of each cycle, with a cycle of 21 days
Arm group label: Adebrelimab+Apatinib+Etoposide

Other name: VP-16

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Female, aged ≥18 years - Expected survival time ≥3 months. - Histologically or cytologically confirmed HER2-negative (IHC 0 or 1+; or IHC 2+ ISH negative) 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 the investigator 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 the study drug can be applied： - Voluntarily join this study, sign the informed consent, have good compliance, and are willing to cooperate with follow-up 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 multiple factors affecting drug administration and absorption； - Participants diagnosed with any other malignant tumor within 5 years before this study, excluding non-melanoma skin cancer that has undergone radical treatment. Basal cell or squamous cell skin cancer or cervical carcinoma in situ and thyroid papillary carcinoma。 - Patients who allergy to any component of the drugs in this protocol; patients with history of immunodeficiency, including HIV positive, HCV, active hepatitis B, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation - History of any cardiac disease, including: (1) arrhythmia requiring medication or clinically significant; (2) myocardial infarction; (3) heart failure; (4) any other cardiac disease judged by the investigator to be unsuitable for participation in this trial, etc. - Pregnant or lactation female patients; females of childbearing age with a positive baseline pregnancy test or unwilling to take effective contraceptive measures during the entire trial period； - According to the investigator's judgment, there are severe accompanying diseases that endanger the patient's safety or affect the completion of the study (including but not limited to uncontrolled severe hypertension, severe diabetes, active infection, etc.).

Gender: Female

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: The Fifth Medical Center of PLA General Hospital

Address:
City: Beijing
Zip: 100071
Country: China

Start date: May 15, 2024

Completion date: December 31, 2026

Lead sponsor:
Agency: Beijing 302 Hospital
Agency class: Other

Source: Beijing 302 Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06418594