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

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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	Female

More Inclusion & Exclusion 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.).

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06418594
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Beijing 302 Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	China
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	HER2-negative Breast Cancer Brain Metastases

Arms & Interventions

Arms

Experimental: Adebrelimab+Apatinib+Etoposide

Adebrelimab: 1200mg， ivgtt，administered on the first day of each cycle, with a cycle of 21 days. Apatinib: 250 mg, oral, once daily, continuous use, with a cycle of 21 days. Etoposide: 50mg/day, oral, administered on days 1-14 of each cycle, with a cycle of 21 days.

Interventions

Drug: - Adebrelimab

Adebrelimab: 1200mg, ivgtt, administered on the first day of each cycle, with a cycle of 21 days

Drug: - Apatinib

Apatinib: 250 mg, oral, once daily, continuous use, with a cycle of 21 days

Drug: - Etoposide

Etoposide: 50mg/day, oral, administered on days 1-14 of each cycle, with a cycle of 21 days

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