SHR-A1921 Combined With Bevacizumab in Triple-negative Breast Cancer With Brain Metastases

Brain Metastasis Clinical Trial

Official title:

SHR-A1921 Combined With Bevacizumab in Triple-negative Breast Cancer With Brain Metastases：a Prospective, Single-arm, Single-center Phase II Clinical Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06210438
• Other study ID #: BCBM-003
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: February 1, 2024
• Est. completion date: June 30, 2026

Study information

• Verified date: December 2023
• Source: Fudan University
• Contact: Biyun Wang
• Phone: 18017312387
• Email: pro_wangbiyun[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phaseⅡ, single-arm study evaluating the efficacy and safety of SHR-A1921 Combined with Bevacizumab in Triple-negative Breast Cancer with Brain Metastases

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years old, both genders

2. ECOG Performance Status of 0-2

3. Pathological tests confirm HR-negative/HER2-negative breast cancer;there is evidence of local recurrence or metastasis;not suitable with curative surgery or radiation therapy;HR negative is defined as: ER-negative and PR-negative, the proportion of positively stained tumor cells in all tumor cells is <10%;HER2- negative is defined as: histologically confirmed to be HER2 IHC (0) or HER2 IHC(1+) or HER2 IHC (2+) and FISH(-)

4. Must have life-expectancy of = 3 months

5. MRI confirmed brain metastases, at least one intracranial parenchymal metastatic lesion with a longest diameter = 1.0 cm without prior radiotherapy;

6. Intraventricular catheter shunting or mannitol?steroid hormone?anticonvulsant drug is allowed before enrollment, but the dose of drug should be stable for at least one week and the neurological symptoms are stable for =1 week

7. Adequate function of major organs meets the following requirements (1)Blood routine

• ANC=1.5×109/L;
• PLT=75×109/L;
• Hb=90 g/L(Allows blood transfusion or the use of medication to ensure that the content of hemoglobin) (2)Coagulation
• INR=1.5,APTT=1.5×ULN (3)Blood biochemistry
• TBIL=1.5 × ULN;
• ALT and AST=3 × ULN (liver metastasis=5.0 × ULN);
• Urea nitrogen = 1.5 × ULN; Cr=1.5 × ULN or creatinine clearance =50 mL / min (Cockcroft-Gault formula) (4)Cardiac ultrasound
• LVEF=50%; (5)12-lead ECG:
• females QTcF interval <470msec and males <450ms;

8. Willing to join the study, sign informed consent, have good compliance and cooperate with follow-up.

Exclusion Criteria:

1. Leptomeningeal or cystic metastases confirmed by MRI or lumbar puncture

2. Presence of third interstitial fluid that cannot be controlled by drainage or other methods (e.g., a large amount of pleural effusion and ascites);

3. Whole brain radiotherapy, chemotherapy, biological targeted therapy, immunotherapy, surgery or endocrine therapy within 2 weeks prior to enrolment

4. Has received prior therapy with bevacizumab and TROP-2 ADC drugs

5. Participation in any other clinical trials within 2 weeks of enrollment

6. Concurrent use of any other Anti-cancer drugs

7. Other malignancies within 5 years, except cured in-situ of uterine cervix carcinoma , skin basal cell carcinoma and squamous-cell carcinoma

8. History of heart disease: (1) Arrhythmias requiring medical treatment or clinical significance, (2) Myocardial infarction, (3) Heart failure, (4)Any heart diseases that investigator believes not suitable for this study

9. History of allergy or hypersensitivity to any of the study drugs or study drug components

10. History of immunodeficiency including HIV-positive, active hepatitis B/C, other acquired, congenital immunodeficiency disease or history of organ transplantation

11. A clear history of neurological or mental disorders, including epilepsy or dementia

12. Pregnant or breastfeeding women. Women of childbearing potential who have a positive pregnancy test or unwilling to use adequate contraception prior to enrollment and for the duration of study participation

13. According to the investigator's judgment, there is a concomitant disease that seriously endangers the safety of subjects or affects the completion of the study (including but not limited to severe hypertension, severe diabetes, active infection, thyroid disease that cannot be controlled by drugs)

14. Any condition which in the investigator's opinion makes the subjects unsuitable for the study participation

Related Conditions & MeSH terms

• Brain Metastasis
• Brain Neoplasms
• Neoplasm Metastasis
• Triple Negative Breast Neoplasms

Intervention

Drug:
• SHR-A1921 + Bevacizumab
SHR-A1921 + Bevacizumab

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CNS ORR	The proportion of patients who have a CR or PR in the CNS, as determined by the Investigator according to RANO-BM criteria	from enrollment to progression or death (for any reason), assessed up to 24 months
Secondary	CNS CBR	CNS clinical benefit rate (CBR) will be defined as the percentage of patients who experience a CR, PR or Stable Disease (SD) for at least 24 weeks.	from enrollment to progression or death (for any reason), assessed up to 24 months
Secondary	Progression-free survival	PFS will be defined as the time from the first dose of treatment to death or disease progression	Up to 2 years
Secondary	Overall survival	OS will be defined as the time from the first dose of treatment to death for any cause	Up to 2 years
Secondary	First progression site	The first lesion to progress	Up to 2 years
Secondary	Safety as assessed by percentage of patients with any Adverse Event	Adverse event according to NCI-CTC AE 5.0	Up to 2 years