T-DXd With or Without Bevacizumab for HER2-low Breast Cancer With Brain Metastasis

NCT07150208 | Not Yet Recruiting Phase 2

• 1 other identifier: SCHBCC- N0102
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

A phase II, open-label, multicenter, randomized controlled trial exploring the efficacy and safety of Trastuzumab Deruxtecan combined with or without Bevicizumab in HER2-low breast cancer with brain metastasis.

Conditions

Breast Cancer With Brain Metastasis; HER2-low Expressing Breast Cancer

Keywords

Breast Cancer with Brain Metastasis; HER2-low Expressing Breast Cancer; Trastuzumab Deruxtecan; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival(PFS)

  Time to progressive disease (according to RECIST1.1)

  12 months

Secondary Outcomes (5)

• CNS Progression-free survival (CNS-PFS)

  12 months

• Objective response rate (ORR)

  12 months

• CNS Objective response rate (CNS-ORR)

  12 months

• Overall survival (OS)

  12 months

• Safety and Tolerability

  12 months

Study Arms (2)

T-DXd

ACTIVE COMPARATOR

T-DXd: 5.4mg/kg intravenously (IV) every 3 weeks (Q3W).

Drug: Trastuzumab Deruxtecan (T-DXd)

T-DXd+Bevacizumab

EXPERIMENTAL

T-DXd: 5.4mg/kg intravenously (IV) every 3 weeks (Q3W). Bevacizumab: 15mg/kg intravenously (IV) every 3 weeks (Q3W).

Drug: Bevacizumab (Bev); Drug: Trastuzumab Deruxtecan (T-DXd)

Interventions

Bevacizumab (Bev) DRUG

Bevacizumab is a drug that targets vascular endothelial growth factor (VEGF) and inhibits tumor angiogenesis, thereby inhibiting tumor growth and spread. In the treatment of breast cancer, Bevacizumab can be used in combination with chemotherapy to improve treatment outcomes and extend patients' progression-free survival and overall survival.

Also known as: HLX04

T-DXd+Bevacizumab

Trastuzumab Deruxtecan (T-DXd) DRUG

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) composed of an anti-HER2 monoclonal antibody (trastuzumab), a cleavable linker, and a topoisomerase I inhibitor (an exatecan derivative). It targets and binds to HER2-positive tumor cells, internalizes, and releases cytotoxic drugs to induce DNA damage and apoptosis. It also has a "bystander effect" that can kill neighboring tumor cells with low HER2 expression, enhancing anti-tumor activity. T-DXd has shown significant efficacy in HER2-positive advanced breast cancer, with key clinical trials (such as DESTINY-Breast03) confirming that its progression-free survival (PFS) and overall survival (OS) are superior to traditional second-line treatments, with a median PFS reaching 28.8 months. Additionally, for HER2-low-expressing (IHC 1+ or 2+/ISH-) metastatic breast cancer (in the DESTINY-Breast04 study), T-DXd can extend PFS and OS, becoming the first targeted therapy to alter the survival outcomes of such patients.

Also known as: DS8201

T-DXd; T-DXd+Bevacizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG score of 0 to 1.
• Expected survival period greater than 12 weeks.
• Histologically confirmed invasive HER2-low expressing breast cancer (specific definition: breast cancer patients with low expression of human epidermal growth factor receptor 2 (HER-2) as determined by pathological testing. Specifically: HER2 IHC 1+ or HER2 IHC++ with FISH/CISH negative. All specimens must be verified by the pathology department of the research participating center.
• Tumor stage: recurrent or metastatic breast cancer; local recurrence must be confirmed by the researcher to be unable to undergo radical surgical resection.
• Patients must have at least one lesion that has not previously received radiation therapy (measurable and/or non-measurable).
• MRI or CT shows brain metastasis and meets one of the following conditions:
• i) Untreated brain parenchymal metastasis found by imaging screening; ii) Previously locally treated stable or progressive brain parenchymal metastasis and meets one of the following conditions:a) Imaging stability ≥4 weeks; b) New brain parenchymal metastasis found by MR or CT.
• Received no more than 2 lines of chemotherapy after metastasis.
• HR-positive patients must have previously received CDK4/6 inhibitor treatment, whether in the adjuvant treatment phase or in the recurrent metastatic phase.
• Never used T-DXd or bevacizumab before.
• The main organ functions are basically normal, meeting the following conditions:
• Blood routine examination standards must comply with: HB≥90g/L (not transfused within 14 days); ANC≥1.5×10\^9/L; PLT≥75×10\^9/L;
• Biochemical examination must comply with the following standards: TBIL≤1.5×ULN (upper limit of normal); ALT and AST≤3×ULN; if there is liver metastasis, ALT and AST≤5×ULN; serum Cr ≤1.5×ULN, endogenous creatinine clearance rate ≥30mL/min.
• Allowed to use mannitol, hormone therapy before enrollment, but the drug treatment dose can be stable for at least one week without the need for an increase.
• Female subjects with reproductive capacity need to use one medically recognized contraceptive method during the study treatment period and for at least 3 months after the last use of the study drug.

You may not qualify if:

• Received more than 2 lines of chemotherapy.
• Used T-DXd or bevacizumab.
• Meningeal metastasis.
• Brain metastasis requiring emergency intervention treatment, or brain metastasis requiring treatment with more than 3mg/d of dexamethasone or equivalent medication.
• Clinical significant or uncontrolled cardiac disease history, including congestive heart failure, angina, myocardial infarction within the past 6 months, or ventricular arrhythmia.
• Ongoing adverse reactions of grade \>1 due to previous treatment. The exception is alopecia or those that the researcher believes should not be excluded. Such cases should be clearly documented in the investigator's notes.
• Pregnant patients.
• History of other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma, or skin squamous cell carcinoma.
• Inability to swallow, chronic diarrhea, and intestinal obstruction, with multiple factors affecting drug intake and absorption.
• Third space fluid accumulation (such as massive pleural effusion and ascites) that cannot be controlled by drainage or other methods.
• Participated in another antitumor drug clinical trial within 4 weeks before the first administration of the study drug.
• Long-term non-healing wounds or incompletely healed fractures.
• Known HBV or HCV infection during the active phase or HBV DNA ≥500, or chronic phase with abnormal liver function.
• Active primary immunodeficiency, known HIV test positive.
• Uncontrolled infection requiring intravenous antibiotics, antiviral drugs, or antifungal drugs.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

MeSH Terms

Interventions

Bevacizumab; trastuzumab deruxtecan

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Zhimin Shao, Professor

CONTACT

08664175590 Ext. 88807; zhimingshao@yahoo.com

Guantian Lang, Doctor

CONTACT

08664175590 Ext. 65277; langguantian@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: August 24, 2025
• First Posted: September 2, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: September 2, 2025

Record last verified: 2025-08

Locations

CN (1)