Breast Cancer MetastaticPhase 1/2NCT06718933
Study of SHR-A1811 Combined With Pyrotinib and Bevacizumab in Advanced Breast Cancer With Brain Metastasis
A Phase 1/2 study testing SHR-A1811, Bevacizumab and Pyrotinib in people with Breast Cancer Metastatic and Breast Cancer Brain Metastases, run by Fudan University at 1 site in China.
Trial summary
In phase Ib, our study is aimed to evaluate the safety and tolerance of SHR-A1811 combined with pyrotinib in breast cancer with brain metastasis, and confirm the recommended phase 2 dose combined with preliminary results of efficacy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer Metastatic, Breast Cancer Brain Metastases
- What is being tested?
- SHR-A1811, Bevacizumab and Pyrotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteChina
- Study dates
- 8 Jan 2025to 28 Feb 2027
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
- No disease progression during prior bevacizumab or EGFR-TKI;
- More than 3 months from the interruption of bevacizumab or EGFR-TKI to disease progression;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Fudan Cancer Hospital
Shanghai, Shanghai Municipality, 200230
Hongxia Wang, Chief physician, +8621-38196379, whx365@126.com
Ting Li, Associate chief physician, +86-18121299346, cinderellaliting@126.com
About this study
Official title: A Prospective, Single-arm, Exploratory, Phase Ib/II Study of SHR-A1811 Combined With Pyrotinib and Bevacizumab in Advanced Breast Cancer With Brain Metastasis.
In phase Ib, our study is aimed to evaluate the safety and tolerance of SHR-A1811 combined with pyrotinib in breast cancer with brain metastasis, and confirm the recommended phase 2 dose combined with preliminary results of efficacy.
In phase II, our study is aimed to evaluate the efficacy and safety of SHR-A1811 combined with pyrotinib and bevacizumab at RP2D in breast cancer with brain metastasis.
- Being tested
- SHR-A1811, Bevacizumab, Pyrotinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHR-A1811Drug
ADC
BevacizumabDrug
bevacizumab biosimilar
PyrotinibDrug
anti-HER2 inhibitor
| Study group | Role | What they receive |
|---|---|---|
| SHR-A1811+pyrotinib | Experimental | In phase Ib, enrolled subjects will received SHR-A1811 combined with pyrotinib at different doses to confirm RP2D and evaluate the safety and tolerance. Receives: Drug: SHR-A1811; Drug: Pyrotinib |
| SHR-A1811+pyrotinib+bevacizumab | Experimental | In phase II, enrolled subjects will received SHR-A1811 combined with pyrotinib and bevacizumab to evaluate the efficacy and safety. Receives: Drug: SHR-A1811; Drug: Bevacizumab; Drug: Pyrotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
RP2D in phase Ib
Recommended phase II dose confirmed by maximum tolerated dose (MTD) and tolerance of subjects.
Measured: From the enrolment of the first subject, to the end of Cycle 6 completion or disease progression or dose discontinuation due to AE in the last enrolled subject
CNS-ORR by investigator in phase II
CNS-ORR is the percentage of evaluable patients with a confirmed investigator-assessed CNS response of CR (complete response) or PR (partial response) per RANO-BM.
Measured: At baseline, at the time point of every 6 weeks
Secondary outcomes (13)
Incidence of dose-limiting toxicity (DLT) in phase Ib
Incidence of DLT
Measured: At the time point of 21 days from first medication
MTD in phase Ib
MTD is the highest dose that does not cause any adverse effects as follows: a) 1 subject experienced the treatment-related serious adverse effects that could endanger the life, cause permanent disability or death; b) 2 of 3 subjects experienced DLTs; c) 1 of the first 3 subjects experienced DLTs, and 1 of the additional 3 subjects at the same dose level experienced DLTs again.
Measured: From the enrolment of the first subject, to the end of Cycle 6 completion or disease progression or dose discontinuation due to AE in the last enrolled subject
Incidence and grade of adverse event (AE) and serious adverse event (SAE) in phase Ib
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. An SAE is defined as any medical event that results in any of the following outcomes: requires inpatient hospitalization or prolongation of existing hospitalization, disability or incapacity, affects ability to work, a life-threatening adverse event or death, a congenital anomaly.
Measured: From the time of informed consent provided to 3 months after the last dose of study therapy
CNS-ORR per RANO-BM in phase Ib
CNS-ORR is the percentage of evaluable patients with a confirmed CNS response of CR (complete response) or PR (partial response) per RANO-BM.
Measured: At baseline, at the time point of every 6 weeks
CNS-ORR per RECIST v1.1 in phase Ib
CNS-ORR is the percentage of evaluable patients with a confirmed CNS response of CR (complete response) or PR (partial response) per RECIST v1.1.
Measured: At baseline, at the time point of every 6 weeks
CNS-DCR in phase Ib
CNS-DCR is the percentage of evaluable patients with a confirmed CNS response of CR (complete response), PR (partial response) or SD (stable disease) per RECIST v1.1.
Measured: At baseline, at the time point of every 6 weeks
DoR in phase Ib
DoR is the time from the date of first detection of objective response (which is subsequently confirmed) until the date of objective radiographic disease progression.
Measured: up to 2 years
CNS-ORR per RECIST v1.1 in phase II
CNS-ORR is the percentage of evaluable patients with a confirmed CNS response of CR (complete response) or PR (partial response) per RECIST v1.1.
Measured: At baseline, at the time point of every 6 weeks
CNS-DCR in phase II
CNS-DCR is the percentage of evaluable patients with a confirmed CNS response of CR (complete response), PR (partial response) or SD (stable disease) per RECIST v1.1.
Measured: At baseline, at the time point of every 6 weeks
DoR in phase II
DoR is the time from the date of first detection of objective response (which is subsequently confirmed) until the date of objective radiographic disease progression.
Measured: up to 2 years
PFS in phase II
PFS is the time from the date of first dose until the date of objective radiographic disease progression or death (by any cause in the absence of progression).
Measured: up to 2 years
OS in phase II
OS is the time from the date of first dose until the date of death by any cause.
Measured: up to 2 years
Safety in phase II
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Percentage of participants who experienced an adverse event and discontinued study drug due to an AE.
Measured: From the time of informed consent provided to 30 days after the last dose of study therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2024
- Study start8 Jan 2025
- Primary completion31 Aug 2026 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 74 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hongxia Wang, Fudan University
- Investigators
- Hongxia Wang, Chief physician, Principal investigator, Fudan UniversityBiyun Wang, Chief physician, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06718933
- Sponsor's protocol ID
- BCBM-004
- Status last verified
- Nov 2024
- First submitted
- 20 Nov 2024
- Last updated
- 6 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Single-arm, Exploratory, Phase Ib/II Study of SHR-A1811 Combined With Pyrotinib and Bevacizumab in Advanced Breast Cancer With Brain Metastasis.
- ClinicalTrials.gov ID
- NCT06718933
- Acronym / sponsor ID
- BCBM-004
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 74 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 8 Jan 2025 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 5 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In phase Ib, our study is aimed to evaluate the safety and tolerance of SHR-A1811 combined with pyrotinib in breast cancer with brain metastasis, and confirm the recommended phase 2 dose combined with preliminary results of efficacy.
In phase II, our study is aimed to evaluate the efficacy and safety of SHR-A1811 combined with pyrotinib and bevacizumab at RP2D in breast cancer with brain metastasis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SHR-A1811+pyrotinib | Experimental | Drug: SHR-A1811, Drug: PyrotinibIn phase Ib, enrolled subjects will received SHR-A1811 combined with pyrotinib at different doses to confirm RP2D and evaluate the safety and tolerance. |
| SHR-A1811+pyrotinib+bevacizumab | Experimental | Drug: SHR-A1811, Drug: Bevacizumab, Drug: PyrotinibIn phase II, enrolled subjects will received SHR-A1811 combined with pyrotinib and bevacizumab to evaluate the efficacy and safety. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (20 listed)
- 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:
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SHR-A1811ADC | Drug | SHR-A1811+pyrotinib, SHR-A1811+pyrotinib+bevacizumab |
| Bevacizumabbevacizumab biosimilar | Drug | SHR-A1811+pyrotinib+bevacizumab |
| Pyrotinibanti-HER2 inhibitor | Drug | SHR-A1811+pyrotinib, SHR-A1811+pyrotinib+bevacizumab |
Primary outcome
RP2D in phase Ib
Time frame: From the enrolment of the first subject, to the end of Cycle 6 completion or disease progression or dose discontinuation due to AE in the last enrolled subject
Recommended phase II dose confirmed by maximum tolerated dose (MTD) and tolerance of subjects.
CNS-ORR by investigator in phase II
Time frame: At baseline, at the time point of every 6 weeks
CNS-ORR is the percentage of evaluable patients with a confirmed investigator-assessed CNS response of CR (complete response) or PR (partial response) per RANO-BM.
13 secondary outcomes
Incidence of dose-limiting toxicity (DLT) in phase Ib
Time frame: At the time point of 21 days from first medication
MTD in phase Ib
Time frame: From the enrolment of the first subject, to the end of Cycle 6 completion or disease progression or dose discontinuation due to AE in the last enrolled subject
Incidence and grade of adverse event (AE) and serious adverse event (SAE) in phase Ib
Time frame: From the time of informed consent provided to 3 months after the last dose of study therapy
CNS-ORR per RANO-BM in phase Ib
Time frame: At baseline, at the time point of every 6 weeks
CNS-ORR per RECIST v1.1 in phase Ib
Time frame: At baseline, at the time point of every 6 weeks
CNS-DCR in phase Ib
Time frame: At baseline, at the time point of every 6 weeks
DoR in phase Ib
Time frame: up to 2 years
CNS-ORR per RECIST v1.1 in phase II
Time frame: At baseline, at the time point of every 6 weeks
CNS-DCR in phase II
Time frame: At baseline, at the time point of every 6 weeks
DoR in phase II
Time frame: up to 2 years
PFS in phase II
Time frame: up to 2 years
OS in phase II
Time frame: up to 2 years
Safety in phase II
Time frame: From the time of informed consent provided to 30 days after the last dose of study therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hongxia Wang, Chief physician principal investigator
Fudan University
Biyun Wang, Chief physician principal investigator
Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SHR-A1811, Bevacizumab and Pyrotinib in people with Breast Cancer Metastatic and Breast Cancer Brain Metastases, 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 8 inclusion and 20 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 6 Feb 2025. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Hongxia Wang, Chief physician (+8621-38196379, whx365@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RP2D in phase Ib (time frame: From the enrolment of the first subject, to the end of Cycle 6 completion or disease progression or dose discontinuation due to AE in the last enrolled subject). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Feb 2025.