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

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

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.

Study Overview

• Status: Completed
• Conditions: HER2-negative Breast Cancer
• Intervention / Treatment: Drug: BGB-290

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Changsha, China, 410013
    • Hunan Cancer Hospital
  • Guangzhou, China, 510060
    • Sun Yat-Sen University Cancer Center
  • Zhejiang, China
    • Zhejiang Cancer Hospital
  • Beijing
    • Beijing, Beijing, China
      • Cancer Hospital Chinese Academy of Medical Science
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Affiliated Tumor Hospital of Harbin Medical University
    • Harbin, Heilongjiang, China, 150000
      • Harbin Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital - Oncology
  • Hunan
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital central South University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Cancer Hospital
    • Xuzhou, Jiangsu, China
      • The Affiliated Hospital Of XuZhou Medical University
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
    • Changchun, Jilin, China, 130022
      • The Second Hospital of Jilin University
    • Changchun, Jilin, China
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning cancer Hospital & Institute
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Center
  • Sichuan
    • Chengdu, Sichuan, China
      • Sichuan Provincial People's Hospital
    • Chengdu, Sichuan, China, 610041
      • West China Hospital ,Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University Cancer Institute & Hospital
  • Yunnan
    • Kunming, Yunnan, China
      • Yunnan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: BeiGene

Publications and helpful links

General Publications

• 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.
• 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. 2022 Dec 2. doi: 10.1007/s10549-022-06785-z. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 22, 2018
• Primary Completion (ACTUAL): October 9, 2020
• Study Completion (ACTUAL): April 14, 2021

Study Registration Dates

• First Submitted: June 19, 2018
• First Submitted That Met QC Criteria: June 28, 2018
• First Posted (ACTUAL): July 2, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 7, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BGB-290-201; CTR20171623 (REGISTRY: National Medical Products Administration- NMPA)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No