Efficacy and Safety of BGB-290 in the Treatment of Metastatic HER2-Negative Breast Cancer Patients With BRCA Mutation in China

Study Overview
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Brief Summary
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This is a Phase 2, open-label, multi-center study of BGB-290 administered orally (PO) twice daily (BID) in adult Chinese patients with advanced HER2(-) breast cancer harboring germline BRCA mutation, which have progressed despite standard therapy, or for which no standard therapy exists.

Official Title
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An Open Label, Multi-Center Phase 2 Study to Evaluate Efficacy and Safety of BGB-290 in the Treatment of Metastatic HER2-Negative Breast Cancer Patients With BRCA Mutation in China

Conditions
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HER2-negative Breast Cancer

Intervention / Treatment
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* Drug: BGB-290


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation Locally advanced or metastatic breast cancer despite standard therapy and the following: Histologically or cytologically confirmed HER2(-) breast cancer (TNBC or estrogen receptor-positive and/or PR+) ≤ 2 prior lines of chemotherapy in advanced or metastatic setting Prior platinum therapy allowed as long as no disease progression while on treatment, or if given in neoadjuvant/adjuvant setting with ≥ 6 months from last platinum to relapse Prior therapy with an anthracycline and/or a taxane in neoadjuvant/adjuvant or metastatic setting Archival tumor tissues will be collected from all patients, if available For HR(+)/HER2(-) breast cancer only: patients must have received and progressed on at least one endocrine therapy either in adjuvant or metastatic setting, or have disease that the treating physician believes to be inappropriate for endocrine therapy Measurable disease as defined per RECIST, version 1.1 Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Adequate hematologic and organ function Exclusion Criteria: Unresolved acute effects of prior therapy of ≥ Grade 2 Prior treatment with a poly[ADP-ribose] polymerase (PARP) inhibitor Chemotherapy, radiotherapy, biologic therapy, immunotherapy, investigational agent, anticancer Chinese medicine, or anticancer herbal remedies ≤ 14 days (or ≤ 5 half lives, if applicable, whichever is shorter) prior to Day 1 of Cycle 1 Major surgical procedure, open biopsy, or significant traumatic injury ≤ 14 days prior to Day 1 of Cycle 1, or anticipation of need for major surgical procedure during the course of the study Diagnosis of myelodysplastic syndrome (MDS) Other diagnosis of malignancy Untreated and/or active brain metastases. Active infection requiring systemic treatment, active viral hepatitis, or active tuberculosis Clinically significant cardiovascular disease Pregnancy or nursing Known history of intolerance to the excipients of the BGB-290 capsule

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Triple-negative breast cancer (TNBC)<br>Locally advanced or metastatic TNBC | Drug: BGB-290<br>* Administered orally<br>* Other names: Pamiparib;|
| Experimental: Cohort 2: HR(+)/HER2(-) breast cancer<br>Locally advanced or metastatic Hormone receptor-positive(HR+) human epidermal growth factor receptor2 Negative(HER2-) breast cancer | Drug: BGB-290<br>* Administered orally<br>* Other names: Pamiparib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) as Assessed by Independent Radiology Review (IRC) | ORR is defined as the percentage of participants who achieved a best overall response of confirmed complete response (CR) or partial response (PR), assessed by IRC per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR as Assessed by Investigator | ORR is defined as the percentage of participants who achieved a best overall response of confirmed complete response (CR) or partial response (PR), assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months) | 
| Progression-free Survival (PFS) as Assessed by IRC and Investigator | PFS is defined as the time from first dose of pamiparib to the first documented disease progression or death due to any cause, assessed by IRC or the investigator | From the first dose of pamiparib to first documentation of disease progression or death (Approximately 2 years and 10 months) | 
| Duration of Response (DOR) as Assessed by IRC | DOR is defined as the time from first determination of a confirmed best overall response until the first documentation of progression or death, whichever comes first, assessed by IRC | From first documentation of confirmed CR or PR to first documentation of disease progression or death (Approximately 2 years and 10 months) | 
| Duration of Response (DOR) as Assessed by the Investigator | DOR is defined as the time from first determination of a confirmed best overall response until the first documentation of progression or death, whichever comes first, assessed by the investigator | From first documentation of confirmed CR or PR to first documentation of disease progression or death (Approximately 2 years and 10 months) | 
| Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | BOR is defined as the percentage of participants with best overall response recorded from the start of the treatment until disease progression or recurrence, assessed by IRC or the investigator. BOR included complete response [CR], partial response [PR], stable disease [SD], disease progression and not evaluable [NE]. | Approximately 2 years and 10 months | 
| Disease Control Rate (DCR) as Assessed by IRC and Investigator | DCR is defined as the percentage of participants who achieved a confirmed BOR of CR, PR, or stable disease (SD), assessed by IRC or the investigator | From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months). | 
| Clinical Benefit Rate (CBR) as Assessed by IRC and Investigator | CBR is defined as percentage of participants with confirmed CR or confirmed PR or a durable SD (SD lasting ≥ 24 weeks), assessed by IRC or the investigator | From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months) | 
| Overall Survival (OS) | OS is defined as time from the first dose of pamiparib to the date of death due to any cause | From the first dose of pamiparib until death (approximately 2 years and 10 months) | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | A TEAE is defined as an adverse event (AE) that had an onset date on or after the first dose of study drug up to 30 days following study drug discontinuation. SAE is defined as any AE that leads to death or is life-threatening. | Up to approximately 2 years and 10 months |