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

HER2-negative Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03575065
• Other study ID #: BGB-290-201
• Secondary ID: CTR20171623
• Status: Completed
• Phase: Phase 2
• Start date: June 22, 2018
• Est. completion date: April 14, 2021

Study information

• Verified date: March 2022
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: April 14, 2021
• Est. primary completion date: October 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-negative Breast Cancer

Intervention

Drug:
• BGB-290
Administered orally

Locations

Country	Name	City	State
China	Cancer Hospital Chinese Academy of Medical Science	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	The second Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha
China	The Second Xiangya Hospital central South University	Changsha	Hunan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	West China Hospital ,Sichuan University	Chengdu	Sichuan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou
China	Affiliated Tumor Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Harbin Cancer Hospital	Harbin	Heilongjiang
China	Shandong Cancer Hospital	Jinan	Shandong
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	Jiangsu Province Cancer Hospital	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Zhejiang Cancer Hospital	Zhejiang
China	Henan Cancer Hospital - Oncology	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

References & Publications (2)

Sun T, Shi Y, Cui J et al; A phase 2 study of pamiparib in the treatment of patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutation. J Clin Oncol 39, 2021 (suppl 15; abstr 1087)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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).
Secondary	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)
Secondary	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)
Secondary	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