Study of SHR-A1811 in HER2-expression Advanced Breast Cancer With Brain Metastases

A Prospective, Open-label Explorative Study of SHR-A1811 in HER2-expression Advanced Breast Cancer With Brain Metastases

This study aimed to evaluate the use of SHR-A1811 in HER2-expression Advanced Breast Cancer patients with brain metastases.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: SHR-A1811; Drug: Pyrotinib; Drug: Bevacizumab; Drug: Adebelizumab

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Min Yan, Professor; Phone Number: +86 15713857388; Email: ym200678@126.com
• Study Contact Backup: Name: HuiMin Lv; Phone Number: +86 15937162120; Email: lvhuimin999@163.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Min Yan, Professor; Phone Number: +86 15713857388; Email: ym200678@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Females and males ≥18 yrs old;
2. Pathologically confirmed HER2-positive or HER2-low advanced breast cancer;
3. At least one measurable intracranial lesion according to RANO-BM criteria, which had not received local treatment;
4. Without prior cranial radiation and had no indication for immediate local treatment or refuse to local treatment;
5. More than 2 weeks from last systemic treatment; patients with new brain lesions after craniocerebral surgery were admitted if no radiotherapy was performed. Patients with HER2-Low disease must not have systemic treatment for brain metastases.
6. Prior HER2-target treatment, endocrine therapy and chemotherapy was allowed;
7. Life expectancy is not less than 6 months.
8. Adequate function of major organs.

Exclusion Criteria:

1. Leptomeningeal involvement;
2. CNS complications requiring emergency neurosurgical intervention (e.g. excision, shunt tube placement);or uncontrolled symptomatic brain metastases;
3. Previous treatment with trastuzumab deruxtecan (DS-8201a) or any other antibody drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase 1 inhibitor;
4. Patients who had progressed on previous HER2 tyrosine kinase inhibitor therapy were excluded from Arm 2, and those who had progressed on previous bevacizumab therapy were excluded from Arm 3 and Arm 5 ,and Arm 6 excludes patients who have progressed on prior PD-1 or PD-L1 therapy;
5. No concurrent antitumor therapy for metastatic cancer other than the study treatment;
6. Antitumor radiotherapy, chemotherapy, surgery, targeted therapy, or immunotherapy within 2 weeks or endocrine therapy within 1 week prior to enrolment;
7. Participated in other drug clinical trials within 4 weeks before admission;
8. History of clinically significant lung disease；
9. Other malignant tumors, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell carcinoma, have been diagnosed in the past five years.
10. According to the judgement of the researchers, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of research (including, but not limited to, severe hypertension, severe diabetes, active infections, etc.).
11. Any other conditions that researchers believe that patients are unsuitable for this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; HER2-positive: SHR-A1811	Drug: SHR-A1811; SHR-A1811: intravenous
Experimental: Arm 2; HER2-positive: SHR-A1811 and pyrotinib	Drug: SHR-A1811; SHR-A1811: intravenous; Drug: Pyrotinib; Pyrotinib: oral
Experimental: Arm 3; HER2-positive: SHR-A1811 and bevacizumab	Drug: SHR-A1811; SHR-A1811: intravenous; Drug: Bevacizumab; Bevacizumab: intravenous
Experimental: Arm 4; HER2-low: SHR-A1811	Drug: SHR-A1811; SHR-A1811: intravenous
Experimental: Arm 5; HER2-low: SHR-A1811 and bevacizumab	Drug: SHR-A1811; SHR-A1811: intravenous; Drug: Bevacizumab; Bevacizumab: intravenous
Experimental: Arm 6; HER2-low: SHR-A1811 and Adebelizumab	Drug: SHR-A1811; SHR-A1811: intravenous; Drug: Adebelizumab; Adebelizumab: intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CNS-ORR by investigator	CNS-ORR was defined as percentage of participants with CNS response assessed by the investigator according to RANO-BM criteria	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR by investigator using RECIST Guideline (Version 1.1)	ORR was defined as percentage of participants with best (confirmed) overall response (BOR) of either CR or PR assessed by the investigator according to RECIST version 1.1	2 months
PFS	PFS was defined as the time from first dose to first documented disease progression (PD) or death from any cause, whichever occurred first	up to 1.5 years
Adverse events	Proportion of participants experienced adverse events during the study period	up to 1.5 years

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2023
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: March 2, 2023
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 15, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; pyrotinib
• Other Study ID Numbers: HNCH-MBC12; HNCH-MBC12-BM04 (Other Identifier: Henan Cancer Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No