BrAin Metastasis in TripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 70 years, with no gender restrictions;

2. ECOG performance score of 0 to 2;

3. Expected survival ≥ 3 months;

4. Patients with unresectable locally advanced, recurrent or metastatic triple-negativebreast cancer who have failed treatment with taxane drugs are included.

5. Ten tissue pathology slides of the primary lesion and/or metastatic lesion (preferably metastatic lesion) can be obtained before the start of treatment forexploratory analysis of molecular indicators related to therapeutic efficacy.

6. Patients must have brain metastases confirmed by MRI, with at least one brainmetastasis lesion that previously has not received radiotherapy and has a longestdiameter of ≥ 1.0 cm; for brain metastasis lesions that have received localtreatment, progression must be confirmed by imaging examination;

7. Cohort A: Patients with brain metastases who have not received central nervoussystem radiotherapy before. Patients with new brain lesions after craniotomy areallowed to be included, provided that they have not received radiotherapy aftersurgery and at least 2 weeks have passed since the surgery;

8. Cohort B: Patients with lesion progression or new lesions after whole brainradiotherapy (WBRT) or stereotactic radiotherapy (SRT). If a patient has multiplecentral nervous system lesions and only one or a few of them have received SRTtreatment, and there are untreated lesions, such patients are still eligible forinclusion in this study;

9. The use of mannitol or hormones for treatment is allowed before enrollment, but thehormone treatment dose should be stable for at least one week without the need foran increase;

10. All patients enrolled are required to have adequate hematologic, hepatic, and renalfunction;

11. Be able to understand the study procedures and sign informed consent.

Exclusion Criteria:

1. Patients with soft meningeal metastases confirmed by MRI or lumbar puncture;

2. Presence of third-space effusion that cannot be controlled by drainage or othermethods (such as large amounts of pleural effusion and ascites);

3. Received whole brain radiotherapy, chemotherapy, or surgery within 2 weeks beforethe treatment with the investigational drug, or received targeted therapy orendocrine therapy within 1 week before the treatment;

4. Previously used monoclonal or bispecific antibodies containing anti-VEGF-A andanti-PD-1/PD-L1/CTLA-4; previously used TROP2 ADC drugs.

5. Participated in other drug clinical trials within 2 weeks before enrollment;

6. Simultaneously receiving any anti-tumor treatment for other tumors;

7. Had other malignant tumors within the past 5 years, excluding cervical carcinoma insitu, basal cell carcinoma or squamous cell carcinoma of the skin, differentiatedthyroid cancer, etc. that have been cured;

8. Patients with severe heart diseases, including: (1) Congestive heart failure (NYHAclass > 2); (2) History of unstable angina pectoris; (3) Myocardial infarctionwithin the past 48 weeks; (4) Clinically significant arrhythmias (excluding atrialfibrillation and paroxysmal supraventricular tachycardia); (5) Any other heartdiseases deemed by the investigator as unsuitable for participation in this trial;

9. Known hypersensitivity to the components of the investigational drug;

10. Uncontrolled serious infection.

11. History of immunodeficiency, including HIV positive, active hepatitis C virusinfection or other acquired or congenital immunodeficiency diseases, or history oforgan transplantation; patients with positive hepatitis B surface antigen (HBsAg)and HBV DNA > 2000 IU/ml or > 104 copies/ml should receive antiviral treatmentaccording to local treatment guidelines and be willing to receive antiviraltreatment throughout the study period; 11. Use of live attenuated vaccines within 28days before randomization, or expected to use such vaccines during the study period (patients are not allowed to receive live attenuated influenza vaccine within 4weeks before randomization, during treatment, and within 5 months after the lastdose of SHR-1316/placebo); 12. Active, known or suspected autoimmune diseases,including but not limited to myasthenia gravis, autoimmune hepatitis, systemic lupuserythematosus, rheumatoid arthritis, inflammatory bowel disease, etc. Type 1diabetes (controlled by insulin), hypothyroidism due to autoimmune thyroiditis thatonly requires hormone replacement therapy, or conditions that are not expected torecur without external stimulation are allowed. Patients with eczema, psoriasis,chronic simple lichen or only with skin manifestations of vitiligo (excludingpsoriatic arthritis) can be enrolled if the rash covers less than 10% of the bodysurface area, the disease is well controlled at baseline and only requireslow-potency topical steroids, and there has been no acute exacerbation of theunderlying disease in the past 12 months (no need for psoralen plus ultravioletradiation [PUVA], methotrexate, retinoids, biologics, oral calcineurin inhibitors,high-potency or oral steroids); 13. History of definite neurological or mentaldisorders, including epilepsy or dementia; 14. Pregnant or lactating women, women ofchildbearing age with positive baseline pregnancy test, or women who are unwillingto take effective contraceptive measures throughout the study period; 15. Accordingto the investigator's judgment, patients with severe concomitant diseases that mayendanger their safety or affect their completion of the study (including but notlimited to uncontrolled severe hypertension, severe diabetes, active infection,thyroid disease, etc.); 16. Any other conditions deemed by the investigator asunsuitable for participation in this study.