Study of Radiotherapy Combined With Cisplatin/Carboplatin, Adebrelimab and Bevacizumab in the Treatment of TNBC-BM. (ABC-R)

A Prospective, Two-arm, Multi-centre, Phase II Clinical Study of Radiotherapy Combined With Cisplatin/Carboplatin, Adebrelimab and Bevacizumab in the Treatment of Patients With Brain Metastasis From Triple-Negative Breast Cancer

This is an open-label, prospective, two-arm, multicenter phase II clinical trial. The aim is to explore the efficacy and safety of radiotherapy combined with cisplatin/carboplatin, adebrelimab, and bevacizumab in patients with triple-negative breast cancer and brain metastases.

Study Overview

• Status: Recruiting
• Conditions: TNBC, Triple Negative Breast Cancer; Brain Metastasases
• Intervention / Treatment: Radiation: Radiation Therapy; Drug: Adebelimab; Drug: Bevacizumab; Drug: Cisplatin or carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Ting LI; Phone Number: +86 13917792964; Email: cinderellaliting@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years and ≤70 years, gender not limited;
2. ECOG score 0-2;
3. Pathologically confirmed HR-negative/HER2-negative breast cancer patients with evidence of local recurrence or metastasis, unsuitable for curative surgical resection or radiotherapy; HR-negative is defined as ER-negative and PR-negative, with positive tumor cells accounting for <10% of all tumor cells;
4. Must not have previously used platinum-based drugs, or must have previously used platinum-based drugs (cisplatin or carboplatin and only one regimen) and meet the following definition of platinum sensitivity: no progression during at least 4 cycles of platinum-based therapy, and subsequent disease progression occurring more than 3 months after the last platinum-based therapy;
5. Expected survival ≥8 weeks;
6. MRI confirms brain metastasis, with at least one previously untreated intracranial brain parenchymal metastatic lesion with a longest diameter ≥1.0 cm;If the brain metastatic lesion has previously undergone radiotherapy, MRI is required to confirm progression after radiotherapy.
7. Provide sufficient fresh tissue specimens or tumor samples (primary lesion and/or metastatic lesions) ≥10 slides before treatment (preferably brain metastatic lesion specimens) for biomarker analysis.

9. Patients receiving mannitol, corticosteroids, or anticonvulsants prior to the first dose are eligible for enrollment if the doses of these concomitant medications have been stable for at least 1 week without escalation, and neurological symptoms have remained stable for ≥1 week.

10. Organ function levels must meet the following requirements:1) Complete blood count:• ANC ≥1.5×10⁹/L;• PLT ≥75×10⁹/L;• Hb ≥90 g/L (blood transfusion or drug treatment is allowed to ensure hemoglobin levels);2) Coagulation function: INR ≤1.5, APTT ≤1.5×ULN; PT not exceeding the upper limit of normal.3) Blood Biochemistry: • TBIL ≤ 1.5 × ULN;• ALT and AST ≤ 3 × ULN (liver metastases ≤ 5.0 × ULN);• Cr ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula);3) Echocardiography: LVEF ≥ 50%;4) 12-lead ECG: Fridricia-corrected QT interval (QTcF) < 470 ms for women and < 450 ms for men; 10. Voluntary participation in this study, signing informed consent, good adherence, and willingness to cooperate with follow-up.

Exclusion Criteria:

1. Leptomeningeal metastases or cystic metastases confirmed by MRI or lumbar puncture;
2. Presence of third-space effusion (e.g., massive pleural effusion and ascites) that cannot be controlled by drainage or other methods;
3. Received whole-brain radiotherapy, chemotherapy, or surgery within 2 weeks prior to treatment with the investigational drug, or received endocrine therapy within one week prior to treatment;
4. Previous use of bevacizumab and PD-1/PD-L1 inhibitors, excluding the following: no disease progression during bevacizumab and PD-1/PD-L1 inhibitor use, investigators believe no drug resistance has been confirmed, and continued use would benefit the subject; short-term bevacizumab use to relieve cerebral edema;
5. Participation in other drug clinical trials within 2 weeks prior to enrollment;
6. Concurrent anti-tumor treatment for any other tumor;
7. History of other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin;
8. History of any heart disease, including: (1) arrhythmia requiring medication or of clinical significance; (2) myocardial infarction; (3) heart failure; (4) any other heart disease deemed unsuitable for participation in this trial by the investigator;
9. A known history of allergy to any component of the medications in this regimen;
10. A history of immunodeficiency, including a positive HIV test, active hepatitis B/C, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
11. A history of a defined neurological or psychiatric disorder, including epilepsy or dementia;
12. Pregnant or lactating women, women of childbearing age with a positive baseline pregnancy test, or patients who do not wish to use effective contraception throughout the trial;
13. In the investigator's judgment, a serious comorbidity that would jeopardize patient safety or affect the patient's ability to complete the study (including but not limited to severe hypertension uncontrolled by medication, severe diabetes, active infection, thyroid disease, etc.);
14. Any other circumstances deemed unsuitable for participation in this study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiotherapy followed by systemic therapy group; Patient who are eligible for inclusion will recieve radiotherapy first, followed by adebrelimab, bevacizumab and Cisplatin/Carplatin.	Radiation: Radiation Therapy; Patients will receive either Fractionated Stereotactic Radiotherapy (FSRT) or Whole Brain Radiotherapy (WBRT), at the discretion of the treating physician based on the number, size, and location of brain metastases.; Drug: Adebelimab; 20mg/kg, IV, D1, Q3W; Drug: Bevacizumab; 7.5mg/kg, IV, D1, Q3W; Drug: Cisplatin or carboplatin; Cisplatin 75mg/m2, IV, D1, Q3W; or carboplatin: AUC=5, IV, D1, Q3W
Experimental: Systemic therapy followed by radiotherapy group; Patient who are eligible for inclusion will recieve adebrelimab, bevacizumab and Cisplatin/Carplatin followed by radiotherapy.	Radiation: Radiation Therapy; Patients will receive either Fractionated Stereotactic Radiotherapy (FSRT) or Whole Brain Radiotherapy (WBRT), at the discretion of the treating physician based on the number, size, and location of brain metastases.; Drug: Adebelimab; 20mg/kg, IV, D1, Q3W; Drug: Bevacizumab; 7.5mg/kg, IV, D1, Q3W; Drug: Cisplatin or carboplatin; Cisplatin 75mg/m2, IV, D1, Q3W; or carboplatin: AUC=5, IV, D1, Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month CNS-PFS rate	The 12-month CNS-PFS rate was used for intracranial efficacy assessment based on RANO-BM, and extracranial efficacy assessment based on RECIST 1.1.	From randomization up to 12 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CNS ORR	ntracranial objective response rate is defined as the proportion of patients who achieve a best overall intracranial response of complete response (CR) or partial response (PR), as assessed by RANO-BM criteria.	Up to 24 months(Efficacy assessments at 6 weeks post-treatment initiation, followed by every 9 weeks thereafter starting from Month 12)
CNS CBR	Clinical benefit rate is defined as the proportion of patients who achieve a best overall intracranial response of complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 24 weeks, as assessed by RANO-BM criteria.	Up to 24 months (Efficacy assessments at 6 weeks post-treatment initiation, followed by every 9 weeks thereafter starting from Month 12)
ORR	Objective response rate is defined as the proportion of patients who achieve a best overall response of complete response (CR) or partial response (PR)	Up to 24 months (Efficacy assessments at 6 weeks post-treatment initiation, followed by every 9 weeks thereafter starting from Month 12)
CBR	clinical benefit rate is defined as the proportion of patients who achieve a best overall response of complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 24 weeks.	Up to 24 months (Efficacy assessments at 6 weeks post-treatment initiation, followed by every 9 weeks thereafter starting from Month 12)
DoR	Duration of response is defined as the time from first documented objective response (CR or PR) until disease progression or death from any cause, whichever occurs first.	From first documented response to progression or death, assessed up to 24 months
CNS PFS	Intracranial progression-free survival is defined as the time from treatment initiation until intracranial disease progression per RANO-BM criteria or death from any cause, whichever occurs first.	From randomization to intracranial progression or death, assessed up to 24 months.
PFS	Progression-free survival is defined as the time from treatment initiation to disease progression or death from any cause, whichever occurs first.	From randomization to progression or death, assessed up to 24 months.
OS	Overall survival is defined as the time from the start of treatment to death from any cause.	From randomization to death, assessed up to 24 months.
Adverse Events (AE)	Adverse events will be assessed and graded according to NCI-CTCAE version 5.0.	From randomization through 30 days after the last dose of study treatment, assessed up to 24 months.
Hopkins Verbal Learning Test-Revised (HVLT-R)	Neurocognitive function assessed using the Hopkins Verbal Learning Test-Revised (HVLT-R).	At screening, 12, 24, 36, 48 weeks, 1.5 years, and 2 years after radiotherapy completion
Functional Assessment of Cancer Therapy-Brain (FACT-Br)	Quality of life assessed using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire.	At screening, within 3 days before each cycle of treatment, and at end of treatment or safety follow-up, assessed up to 24 months
Mini-Mental State Examination (MMSE)	Neurocognitive function assessed using the Animal Verbal Fluency Test.	At screening, 12, 24, 36, 48 weeks, 1.5 years, and 2 years after radiotherapy completion
Animal Verbal Fluency Test	Animal Oral Vocabulary Association Test	From enrollment to the end of treatment at 24 months，evaluations were conducted at screening, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 1.5 years, and 2 years after completion of radiotherapy.
Trail Making Test (TMT-A/TMT-B)	Neurocognitive function assessed using the Trail Making Test (TMT-A/TMT-B)	At screening, 12, 24, 36, 48 weeks, 1.5 years, and 2 years after radiotherapy completion
EORTC QLQ-C30	Quality of life assessed using the EORTC Core Quality of Life Questionnaire (QLQ-C30), scoring from 0 to 100. This questionnaire is for functional and global quality of life scales, higher scores mean a better level of functioning. For symptom-oriented scales, a higher score means more severesymptoms.	At screening, within 3 days before each cycle of treatment, and at end of treatment or safety follow-up, assessed up to 24 months
EORTC QLQ-BN20	Quality of life assessed using the EORTC Quality of Life Questionnaire for Brain Neoplasms (QLQ-BN20). This aims to evaluate the effects of the tumour and its treatment on symptoms, functions and health-related quality of life (HRQoL) of brain tumour patients. The scale scoring form 0 to 100, and a higher score generally indicates more severe symptoms and poorer quality of life.	At screening, within 3 days before each cycle of treatment, and at end of treatment or safety follow-up, assessed up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Biomarker Analysis	Tumor tissue (≥10 unstained slides or fresh tissue specimens), blood (8 mL of clotted blood, 8 mL of anticoagulated blood), cerebrospinal fluid (8 mL), urine (20 mL ), and stool samples (5 g) will be collected for exploratory cytological and multi-omics analyses to identify biomarkers associated with treatment response and resistance to radiotherapy combined with systemic therapy.	At baseline, after Cycle 2 (each cycle is 21 days), and at disease progression or treatment discontinuation (up to 24 months)

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 26, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: radiotherapy; Bevacizumab; TNBC; adebrelimab; brain metastatic
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Skin and Connective Tissue Diseases; Triple Negative Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Platinum Compounds; Bevacizumab; Carboplatin; Cisplatin; Radiotherapy
• Other Study ID Numbers: 2510331-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared. The informed consent states that participants' records will be kept in a locked filing cabinet and accessed only by the research team, with access granted to regulatory authorities or the ethics committee solely for on-site monitoring purposes. The consent does not include provision for sharing de-identified individual participant data with other researchers or depositing data in public repositories.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No