Clinical trial NCT03575065: Efficacy and Safety of BGB-290 in the Treatment of Metastatic HER2-Negative Breast Cancer Patients With BRCA Mutation in China
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HER2-negative Breast Cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-07-02
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Objective Response Rate (ORR) as Assessed by Independent Radiology Review (IRC)
timeFrame: From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 4 months)
Secondary outcomes:
measure: ORR as Assessed by Investigator
timeFrame: From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months)
measure: Progression-free Survival (PFS) as Assessed by IRC and Investigator
timeFrame: From the first dose of pamiparib to first documentation of disease progression or death (Approximately 2 years and 10 months)
measure: Duration of Response (DOR) as Assessed by IRC
timeFrame: From first documentation of confirmed CR or PR to first documentation of disease progression or death (Approximately 2 years and 10 months)
measure: Duration of Response (DOR) as Assessed by the Investigator
timeFrame: From first documentation of confirmed CR or PR to first documentation of disease progression or death (Approximately 2 years and 10 months)
measure: Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator
timeFrame: Approximately 2 years and 10 months
measure: Disease Control Rate (DCR) as Assessed by IRC and Investigator
timeFrame: From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months).
measure: Clinical Benefit Rate (CBR) as Assessed by IRC and Investigator
timeFrame: From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months)
measure: Overall Survival (OS)
timeFrame: From the first dose of pamiparib until death (approximately 2 years and 10 months)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
timeFrame: Up to approximately 2 years and 10 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University Wuhan
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Cancer Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang University College of Medicine Second Affiliated Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Xu B, Zhang QY, Yang H, Gu T, Zhang K, Liang J, Qiu JJ, Yang R, Zhang L, Mu S, Sun J, Huang V, Dong M. An Open-Label, Multicenter, Phase 2 Study to Evaluate the Antitumor Activity and Safety of Pamiparib in the Treatment of Metastatic HER2-Negative Breast Cancer Patients With BRCA Mutation in China. Chinese Society of Clinical Oncology. 2018.
citation: Xu B, Sun T, Shi Y, Cui J, Yin Y, Ouyang Q, Liu Q, Zhang Q, Chen Y, Wang S, Wang X, Tong Z, Zhong Y, Wang J, Yan M, Yan X, Wang C, Feng J, Wang X, Hu G, Cheng Y, Ge R, Zhu Z, Zhang W, Shao Z. Pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutations: a phase II study. Breast Cancer Res Treat. 2023 Feb;197(3):489-501. doi: 10.1007/s10549-022-06785-z. Epub 2022 Dec 2.