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Breast Cancer With Brain MetastasisPhase 2THUMBNCT07150208

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

A Phase 2 study testing Bevacizumab (Bev) and Trastuzumab Deruxtecan (T-DXd) in people with Breast Cancer With Brain Metastasis and HER2-low Expressing Breast Cancer, run by Fudan University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years, women only
What is being tested?
Bevacizumab (Bev) and Trastuzumab Deruxtecan (T-DXd)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
1 siteChina
Study dates
20 Oct 2025to Sep 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • Subjects voluntarily join this study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Who cannot join

  • 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.
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  • 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.
  • History of (non-infectious) ILD/pneumonia requiring steroids, currently having ILD/pneumonia, or unable to exclude suspected ILD/pneumonia on imaging during screening.
  • Pulmonary criteria:
  • Clinically significant pulmonary comorbidities, including but not limited to any underlying pulmonary disease (e.g., pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.) within 3 months of study recruitment.
  • Any autoimmune disease, connective tissue disease, or inflammatory disease (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.) with recorded or suspected pulmonary involvement during screening. All detailed information about the disease should be recorded in the CRF for participants in the study.
  • Previous total pneumonectomy.
  • Allergic constitution, or known history of allergy to any component of the study regimen, or allergic to other monoclonal antibodies.
  • History of gastrointestinal bleeding within the past 6 months or a clear tendency for gastrointestinal bleeding, such as: esophageal varices at risk of bleeding, local active ulcer lesions, fecal occult blood ≥ (++) not eligible for enrollment; if fecal occult blood (+), gastroscopy is required;
  • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days before participating in this study;
  • Urinalysis shows urine protein ≥++ or confirmed 24-hour urine protein quantitative >1.0g;
  • Hypertension, and blood pressure cannot be lowered to the normal range with antihypertensive drugs (systolic blood pressure >140mmHg, diastolic blood pressure >90mmHg).
  • Substance abuse or medical conditions that the researcher believes may interfere with the subject's participation in the clinical study or the assessment of the clinical study results.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Zhimin Shao, Professor contact

08664175590 Ext. 88807

zhimingshao@yahoo.com

Guantian Lang, Doctor contact

08664175590 Ext. 65277

langguantian@126.com

China1 site, 1 recruiting

  • Fudan University Shanghai Cancer Center

    Shanghai, 200032

    Zhimin Shao, Professor, 8664175590 Ext. 88807, zhimingshao@yahoo.com

    Guantian Lang, MD, langguantian@126.com

    Recruiting

Other trials in China

About this study

Official title: Trastuzumab Deruxtecan With or Without Bevacizumab for HER2-low Unresectable and/or Metastatic Breast Cancer With Brain Metastasis: A Multicenter, Randomized, Open Label, Phase II Trial (THUMB Trial)

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.

Read the detailed description

This is a Phase II, open-label, multicenter, randomized controlled trial (THUMB study) comparing the efficacy and safety of trastuzumab deruxtecan (T-DXd) with or without bevacizumab for HER2-low expressing breast cancer with brain metastases. Patients receiving treatment in the metastatic setting must not have received more than 3 lines of therapy (HR-positive patients must have received a CDK4/6 inhibitor). Participants are randomized in a 1:1 ratio to receive treatment with T-DXd combined or not combined with bevacizumab.

Being tested
Bevacizumab (Bev), Trastuzumab Deruxtecan (T-DXd)
Keywords
Breast Cancer with Brain Metastasis, HER2-low Expressing Breast Cancer, Trastuzumab Deruxtecan, Bevacizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bevacizumab (Bev)Drug

    Also called HLX04

    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.

  • Trastuzumab Deruxtecan (T-DXd)Drug

    Also called DS8201

    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.

Study groups in NCT07150208
Study groupRoleWhat they receive
T-DXdActive comparatorT-DXd: 5.4mg/kg intravenously (IV) every 3 weeks (Q3W).
Receives: Drug: Trastuzumab Deruxtecan (T-DXd)
T-DXd+BevacizumabExperimentalT-DXd: 5.4mg/kg intravenously (IV) every 3 weeks (Q3W). Bevacizumab: 15mg/kg intravenously (IV) every 3 weeks (Q3W).
Receives: Drug: Bevacizumab (Bev); Drug: Trastuzumab Deruxtecan (T-DXd)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival(PFS)

    Time to progressive disease (according to RECIST1.1)

    Measured: 12 months

Secondary outcomes (5)

  1. CNS Progression-free survival (CNS-PFS)

    Time from enrollment to the first radiographic documented disease progression (PD) of all CNS target lesions (RANO-BM criteria) or death from any cause without progression was recorded.

    Measured: 12 months

  2. Objective response rate (ORR)

    Partial response is defined as a decrease by 30% or more in sums of longest diameter of measurable target lesions

    Measured: 12 months

  3. CNS Objective response rate (CNS-ORR)

    The proportion of patients with complete response (CR) and partial response (PR) evaluated as the best response observed from enrollment to progression of all CNS target lesions assessed according to RANO-BM criteria among the total number of patients who could be evaluated.

    Measured: 12 months

  4. Overall survival (OS)

    Time from the enrollment to death of any cause

    Measured: 12 months

  5. Safety and Tolerability

    Safety and Tolerability Will be Assessed According to Standard (CTCAE Version 5.0) Toxicity Reporting Criteria.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Sep 2025
  2. Study start20 Oct 2025
  3. Primary completionSep 2027 (estimated)
  4. Study completionSep 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Parallel Assignment
Masking
None (open label)
Enrolment
140 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07150208
Sponsor's protocol ID
SCHBCC- N0102
Acronym
THUMB
Status last verified
Sep 2026
First submitted
24 Aug 2025
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab (Bev) and Trastuzumab Deruxtecan (T-DXd) in people with Breast Cancer With Brain Metastasis and HER2-low Expressing Breast Cancer, run by Fudan University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Zhimin Shao, Professor (08664175590 Ext. 88807, zhimingshao@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival(PFS) (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07150208.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.

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