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

Phase 2

Completed

• Conditions: HER2-negative Breast Cancer
• Interventions: Drug: BGB-290

• Registration Number: NCT03575065
• Lead Sponsor: BeiGene

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-06-19
• Study Start: 2018-06-22
• Study First Submitted QC: 2018-06-28
• Study First Posted: 2018-07-02
• Primary Completion: 2020-10-09
• Study Completion: 2021-04-14
• Results First Submitted: 2022-03-28
• Results First Submitted QC: 2022-03-28
• Results First Posted: 2022-09-07
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-23
• Last Update Posted: 2024-10-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

1. Confirmed deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation

2. Locally advanced or metastatic breast cancer despite standard therapy and the following:

   1. Histologically or cytologically confirmed HER2(-) breast cancer (TNBC or estrogen receptor-positive and/or PR+)
   2. ≤ 2 prior lines of chemotherapy in advanced or metastatic setting
   3. 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
   4. Prior therapy with an anthracycline and/or a taxane in neoadjuvant/adjuvant or metastatic setting
   5. Archival tumor tissues will be collected from all patients, if available
   6. 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

3. Measurable disease as defined per RECIST, version 1.1

4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

5. Adequate hematologic and organ function

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Exclusion Criteria

1. Unresolved acute effects of prior therapy of ≥ Grade 2
2. Prior treatment with a poly[ADP-ribose] polymerase (PARP) inhibitor
3. 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
4. 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
5. Diagnosis of myelodysplastic syndrome (MDS)
6. Other diagnosis of malignancy
7. Untreated and/or active brain metastases.
8. Active infection requiring systemic treatment, active viral hepatitis, or active tuberculosis
9. Clinically significant cardiovascular disease
10. Pregnancy or nursing
11. Known history of intolerance to the excipients of the BGB-290 capsule

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: Triple-negative breast cancer (TNBC)	BGB-290	Locally advanced or metastatic TNBC
Cohort 2: HR(+)/HER2(-) breast cancer	BGB-290	Locally advanced or metastatic Hormone receptor-positive(HR+) human epidermal growth factor receptor2 Negative(HER2-) breast cancer

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) as Assessed by Independent Radiology Review (IRC)	From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 4 months)	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)

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) as Assessed by IRC and Investigator	From the first dose of pamiparib to first documentation of disease progression or death (Approximately 2 years and 10 months)	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
Duration of Response (DOR) as 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)	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
Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator	Approximately 2 years and 10 months	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 \[NE\].
Clinical Benefit Rate (CBR) as Assessed by IRC and Investigator	From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months)	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
Overall Survival (OS)	From the first dose of pamiparib until death (approximately 2 years and 10 months)	OS is defined as time from the first dose of pamiparib to the date of death due to any cause
Duration of Response (DOR) as 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)	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
Number of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)	Up to approximately 2 years and 10 months	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.
ORR as Assessed by Investigator	From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months)	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)
Disease Control Rate (DCR) as Assessed by IRC and Investigator	From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months).	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

Trial Locations

Locations (20)

Cancer Hospital Chinese Academy of Medical Sciences; 🇨🇳 Beijing, Beijing, China

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North); 🇨🇳 Guangzhou, Guangdong, China

Sun Yat Sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China

Harbin Medical University Cancer Hospital; 🇨🇳 Harbin, Heilongjiang, China

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China

Zhongnan Hospital of Wuhan University Wuhan; 🇨🇳 Wuhan, Hubei, China

Xiangya Hospital of Central South University; 🇨🇳 Changsha, Hunan, China

Jiangsu Province Hospital; 🇨🇳 Nanjing, Jiangsu, China

The Second Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

Liaoning Cancer Hospital and Institute; 🇨🇳 Shenyang, Liaoning, China

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital; 🇨🇳 Chengdu, Sichuan, China

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, Tianjin, China

Zhejiang University College of Medicine Second Affiliated Hospital; 🇨🇳 Hangzhou, Zhejiang, China

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou, Fujian, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China

Jiangsu Province Cancer Hospital; 🇨🇳 Nanjing, Jiangsu, China

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China