Clinical trial NCT06718933: Study of SHR-A1811 Combined With Pyrotinib and Bevacizumab in Advanced Breast Cancer With Brain Metastasis
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer Metastatic
Breast Cancer Brain Metastases
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-12-05
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

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.


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.

Primary outcomes:
measure: RP2D in phase Ib
timeFrame: 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
measure: CNS-ORR by investigator in phase II
timeFrame: At baseline, at the time point of every 6 weeks
Secondary outcomes:
measure: Incidence of dose-limiting toxicity (DLT) in phase Ib
timeFrame: At the time point of 21 days from first medication
measure: MTD in phase Ib
timeFrame: 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
measure: Incidence and grade of adverse event (AE) and serious adverse event (SAE) in phase Ib
timeFrame: From the time of informed consent provided to 3 months after the last dose of study therapy
measure: CNS-ORR per RANO-BM in phase Ib
timeFrame: At baseline, at the time point of every 6 weeks
measure: CNS-ORR per RECIST v1.1 in phase Ib
timeFrame: At baseline, at the time point of every 6 weeks
measure: CNS-DCR in phase Ib
timeFrame: At baseline, at the time point of every 6 weeks
measure: DoR in phase Ib
timeFrame: up to 2 years
measure: CNS-ORR per RECIST v1.1 in phase II
timeFrame: At baseline, at the time point of every 6 weeks
measure: CNS-DCR in phase II
timeFrame: At baseline, at the time point of every 6 weeks
measure: DoR in phase II
timeFrame: up to 2 years
measure: PFS in phase II
timeFrame: up to 2 years
measure: OS in phase II
timeFrame: up to 2 years
measure: Safety in phase II
timeFrame: From the time of informed consent provided to 30 days after the last dose of study therapy
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan Cancer Hospital
state: Shanghai
Study officials:
affiliation: Fudan University
name: Hongxia Wang, Chief physician
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Biyun Wang, Chief physician
role: PRINCIPAL_INVESTIGATOR
References: