Study of SHR-A1811 Combined With Pyrotinib and Bevacizumab in Advanced Breast Cancer With Brain Metastasis

NCT06718933 | Recruiting Phase 1

• 1 other identifier: BCBM-004
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer Metastatic; Breast Cancer Brain Metastases

Outcome Measures

Primary Outcomes (2)

• RP2D in phase Ib

  Recommended phase II dose confirmed by maximum tolerated dose (MTD) and tolerance of subjects.

  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.

  At baseline, at the time point of every 6 weeks

Secondary Outcomes (13)

• Incidence of dose-limiting toxicity (DLT) in phase Ib

  At the time point of 21 days from first medication

• MTD in phase Ib

  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

  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

  At baseline, at the time point of every 6 weeks

• CNS-ORR per RECIST v1.1 in phase Ib

  At baseline, at the time point of every 6 weeks

Study Arms (2)

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.

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.

Drug: SHR-A1811; Drug: Bevacizumab; Drug: Pyrotinib

Interventions

SHR-A1811 DRUG

ADC

SHR-A1811+pyrotinib; SHR-A1811+pyrotinib+bevacizumab

Bevacizumab DRUG

bevacizumab biosimilar

SHR-A1811+pyrotinib+bevacizumab

Pyrotinib DRUG

anti-HER2 inhibitor

SHR-A1811+pyrotinib; SHR-A1811+pyrotinib+bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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);

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan Cancer Hospital

Shanghai, Shanghai Municipality, 200230, China

RECRUITING

MeSH Terms

Interventions

Bevacizumab; pyrotinib

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hongxia Wang, Chief physician

  Fudan University

  PRINCIPAL INVESTIGATOR

• Biyun Wang, Chief physician

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hongxia Wang, Chief physician

CONTACT

+8621-38196379; whx365@126.com

Ting Li, Associate chief physician

CONTACT

+86-18121299346; cinderellaliting@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: December 5, 2024
• Study Start: January 8, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: February 6, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)