Combining SHR-A1811, Pyrotinib, and Bevacizumab for Advanced Breast Cancer with Brain Metastasis

A Prospective, Single-arm, Exploratory, Phase Ib/II Study of SHR-A1811 Combined With Pyrotinib and Bevacizumab in Advanced Breast Cancer With Brain Metastasis.

This study is testing a new combination of three drugs to see if it can help people with advanced breast cancer that has spread to the brain feel better and improve their treatment outcomes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: bevacizumab, trastuzumab, chemotherapy, pyrotinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06718933 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of SHR-A1811 when combined with pyrotinib and bevacizumab in patients with advanced breast cancer that has spread to the brain. In the first phase, the focus is on determining the recommended dose and assessing safety, while the second phase aims to confirm the treatment's effectiveness at this dose. Participants will be closely monitored for any adverse effects and overall treatment response.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with confirmed brain metastasis from breast cancer and a life expectancy of at least three months.

Not a fit: Patients with leptomeningeal metastasis or uncontrolled third space fluid conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with advanced breast cancer and brain metastases.

How similar studies have performed: While this specific combination is novel, similar approaches in treating brain metastases from breast cancer have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

* More than 18 years old;
* ECOG PS Score: 0\~2;
* Patients must have a life expectancy ≥ 3 months;
* Brian metastasis confirmed by MRI, at least one measurable brain lesion based on RANO-BM with no prior radiotherapy;
* Mannitol or hormone therapy is allowed to use for brain metastasis before enrolment, but treatment dosage should be stable for one week and not need to be increased;
* Adequate organ function and marrow function;
* Has recovered from any AEs (≤ grade 1) related to prior anti-tumour treatments before first dose of study therapy, except: a. alopecia; b. hyperpigmentation;
* Willing to join in this study, able to provide written informed consent, good compliance and willing to cooperate with follow-up.

Exclusion Criteria:

* Has leptomeningeal metastasis or cystic metastatic lesions confirmed by MRI or lumbar puncture;
* Existence of third space fluid (e.g. massive ascites, pleural effusion, pericardial effusion) that is not well controlled by effective methods, e.g. drainage;
* Has CNS complications with the need for emergency intervention, or brain metastasis with poorly controlled symptoms by hormone or dehydration therapy, such as uncontrollable intracranial hypertension, mental disorder or epilepsy;
* Prior bevacizumab or EGFR-TKI is allowed, but should meet the following requirements at the same time:

  1. No disease progression during prior bevacizumab or EGFR-TKI;
  2. More than 3 months from the interruption of bevacizumab or EGFR-TKI to disease progression;
* Has received whole brain radiotherapy, chemotherapy, surgery within 2 weeks before first dose of study therapy; has received trastuzumab-based therapy or endocrine therapy within one week before first dose of study therapy; has received palliative radiotherapy for bone metastasis within 2 weeks before first dose of study therapy;
* Has known clinically significant lung disease, that is, moderate-to-severe lung disease which severely affects respiratory function, including but not limited to: idiopathic pulmonary fibrosis, pneumonitis. Prior ≥ grade 3 interstitial lung disease is not allowed to enrolment;
* Has received full-dose anticoagulants or thrombolytics within 10 days before enrolment, or non-steroid anti-inflammatory drugs with platelet inhibition (except low-dose aspirin (≤325mg qd) for preventive use);
* Existence of unhealed wound, active gastric ulcer, and other diseases which may cause haemorrhage risk (e.g., prior major operation within 4 weeks before enrolment, prior arterial or venous thrombotic event within one year before enrolment, prior cerebralvascular accident);
* Has known hereditary haemorrhagic tendency or coagulation disorder;
* Has joined in other clinical drug trials within 2 weeks before enrolment;
* Use of other antitumor systemic treatment during the study at the same time, except bisphosphonates for the treatment of bone metastasis or osteoporosis prevention;
* Other malignancy within prior 5 years unless curatively treated with no evidence of disease for at least recent 3 years, except: curatively treated in situ cancer of the cervix, skin basal cell carcinoma or skin squamous cell carcinoma;
* Cardiac insufficiency, including but not limited to: congestive heart failure, transmural myocardial infarction, angina which needs drug treatments, clinically significant valvulopathy and high-risk arrhythmia, or QTc abnormity with clinical significance in ECG examination during the screening period (corrected QTc \>450 msec \[male\] or QTc \>470 msec \[female\] under the resting state);
* Uncontrolled hypertension (under the resting state: systolic pressure \>160mmHg or diastolic pressure \>100mmHg);
* Other diseases which may affect study results, including but not limited to: 1) known history of immunodeficiency, including HIV-positive, other acquired or innate immunodeficient disease, or known history of organ transplantation; 2) HBsAg-positive and HBV DNA≥1000 IU/mL, or HCV antibody-positive, or treponema pallidum antibody-positive; 3) hypersensitivity to study therapy or any of its excipients; 4) severe infection requiring antibiotics, antiviral or antifungal treatment;
* Female patients during the gestation or suckling period, of childbearing potential and pregnancy test-positive, or unwilling to use an effective method of contraception during the whole study;
* Inability to swallow, intestinal obstruction or existence of other factors affecting medication and absorption;
* Any other conditions not appropriate for study enrolment in the opinion of the investigator.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan Cancer Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Hongxia Wang, Chief physician — Fudan University
• Study coordinator: Hongxia Wang, Chief physician

Conditions Breast Cancer Metastatic; Breast Cancer Brain Metastases