A Pivotal Phase II Clinical Trial of Utidelone Injection Plus Capecitabine in HER2-negative Breast Cancer Patients With Brain Metastases

Inclusion Criteria:

1. Have histologically confirmed HER2-negative metastatic breast cancer. HER2-negativedefined as immunohistochemical (IHC) score of 0 or 1+, or IHC2+ with negative HER2expression on in situ hybridization (ISH).

2. Based on screening contrast-enhanced brain MRI, patients must have at least onemeasurable intracranial lesion according to RECIST 1.1 (≥1.0 cm in size) .

3. Male or female aged ≥18 years.

4. ECOG PS 0 or 1.

5. Have a life expectancy of at least 3 months.

6. Have adequate baseline hematologic parameters.

7. Have adequate hepatic and renal function.

8. ≤ 3 prior lines of chemotherapy in advanced or metastatic setting.

9. Women of childbearing potential, unless hysterectomy or oophorectomy orpostmenopausal for at least 12 consecutive months, must use an effective method ofavoiding pregnancy (including oral, transdermal, or implanted contraceptives [anyhormonal method in conjunction with a secondary method], intrauterine device, femalecondom with spermicide, diaphragm with spermicide, absolute sexual abstinence, useof condom with spermicide by sexual partner or sterile [at least 6 months prior tostudy drug administration] sexual partner) for at least 4 weeks prior to study drugadministration, during study and up to 6 months following the last dose of studydrug. Cessation of birth control after this point should be discussed with aresponsible physician. Investigator will discuss with patient on the above pointsand the patient agreement will be documented in the source document. Theinvestigator should ensure that the patient is using an effective method of avoidingpregnancy as per protocol. In case of Male patients: Either patient partners orpatients themselves must use an effective method of avoiding pregnancy for at least 4 weeks prior to study drug administration, during study and up to 6 monthsfollowing the last dose.

10. Patients must be able to follow the study visit schedule, and must be able of signand give informed consent in accordance with institutional review board.

Exclusion Criteria:

1. Leptomeningeal metastasis confirmed by MRI and/or cerebrospinal fluid cytology.

2. Any intracranial lesion thought to require immediate local therapy, including (butnot limited to) a lesion in an anatomic site where increase in size or possibletreatment-related edema may pose risk to patient (e.g. brain stem lesions).

3. Have poorly controlled (> 1/week) generalized or complex partial seizures, ormanifest neurologic progression due to brain metastases notwithstanding CNS-directedtherapy.

4. Had evidence of intracranial hemorrhage within 3 months before study treatment.

5. Had evidence of hemoptysis within 6 months before study treatment. Or bleeding orevidence of coagulopathy within 4 weeks before study treatment.

6. Undergone major surgical procedures within 4 weeks or not fully recovered fromsurgery before study treatment.

7. Patients who have received anti-tumor therapies less than 2 weeks before the firstdose of investigational product, including endocrine therapy, chemotherapy,radiotherapy, biotherapy, targeted therapy, immunotherapy or antibody-drug conjugatetherapy.

8. Persistent toxicities caused by previous antitumor therapy (excluding alopecia), notyet improved to CTCAE v5.0 grade ≤ 1 or baseline.

9. Patients with neuropathy> grade 1.

10. Known hypersensitivity to any components of the investigational product.

11. Known deficiency of dihydropyrimidine dehydrogenase (DPD).

12. This applies only to the combination cohort and does not apply to the monotherapycohort. For patients with previous capecitabine treatment, the prior use ofcapecitabine meets any of the following criteria: A) The best response during priorcapecitabine combination therapy or monotherapy is Progressive Disease (PD); B) Havereceived capecitabine treatment within 6 months prior to the first study treatment.

13. Patients who are pregnant (positive pregnancy test) or lactating.

14. Patients with other malignancies over the past 5 years, except for inactive tumorswith good prognosis, including resected basal cell and squamous cell carcinoma ofthe skin, in-situ carcinoma of the cervix, or papillary thyroid cancer.

15. Patients who are particpating in other interventional studies or who are receivingother study treatments (patients who have discontinued other investigationaltreatments and are in follow-up are eligible for enrollement in this study).

16. Known active or uncontrolled hepatitis B infection, active syphilis, or HIVinfection that is not well controlled; or positive for hepatitis B virus based onthe evaluation of results of tests for hepatitis B (HBsAg, anti-HBs, anti-HBc, orHBV DNA) infection at screening.

17. With a history of severe or uncontrolled diseases.

18. Autoimmune diseases requiring treatment with systemic glucocorticoids.

19. Not able to perform contrast-enhanced brain MRI or known contraindications to MRIgadolinium contrast, such as cardiac pacemaker, shrapnel, or eye foreign body.

20. Patients with a history of other systemic severe diseases or abnormal laboratoryfindings that would, in the Investigator's judgment, be inappropriate for thisstudy.