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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Brain Metastasis; TNBC
• Intervention / Treatment: Drug: SHR-A1921 + Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Biyun Wang; Phone Number: 18017312387; Email: pro_wangbiyun@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
      • Contact: Biyun Wang; Phone Number: +86-021-64175590; Email: pro_wangbiyun@163.com
      • Principal Investigator: Biyun Wang

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-A1921 + Bevacizumab	Drug: SHR-A1921 + Bevacizumab; SHR-A1921 + Bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by percentage of patients with any Adverse Event	Adverse event according to NCI-CTC AE 5.0	Up to 2 years
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
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
Overall survival	OS will be defined as the time from the first dose of treatment to death for any cause	Up to 2 years
First progression site	The first lesion to progress	Up to 2 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Biyun Wang, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: January 17, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: BCBM-003

Drug and device information, study documents

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