Clinical Trial Finder

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.

Arms

Experimental: SHR-A1811+pyrotinib

In phase Ib, enrolled subjects will received SHR-A1811 combined with pyrotinib at different doses to confirm RP2D and evaluate the safety and tolerance.

Experimental: SHR-A1811+pyrotinib+bevacizumab

In phase II, enrolled subjects will received SHR-A1811 combined with pyrotinib and bevacizumab to evaluate the efficacy and safety.

Interventions

Drug: - SHR-A1811

ADC

Drug: - Bevacizumab

bevacizumab biosimilar

Drug: - Pyrotinib

anti-HER2 inhibitor