HER2-negative Breast Cancer
Conditions
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.
Interventions
DRUGBGB-290
Administered orally
Sponsors
BeiGene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 \[NE\]. |
| 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) |
| 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 |
| 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. |
| 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 |
Countries
China
Participant flow
Recruitment details
A total of 88 participants were recruited in China.
Participants by arm
| Arm | Count |
|---|---|
| TNBC Participants received 60 mg pamiparib BID orally in 28-day cycles until disease progression, unacceptable toxicity, death, withdrawal of consent or study termination by sponsor | 62 |
| HR(+)/HER2(-) Breast Cancer Participants received 60 mg pamiparib BID orally in 28-day cycles until disease progression, unacceptable toxicity, death, withdrawal of consent or study termination by sponsor | 26 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 31 | 12 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Sponsor's Decision | 28 | 13 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | TNBC | HR(+)/HER2(-) Breast Cancer | Total |
|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 8.56 | 46.4 years STANDARD_DEVIATION 10.75 | 45.8 years STANDARD_DEVIATION 9.2 |
| Race/Ethnicity, Customized Asian - Chinese | 62 Participants | 26 Participants | 88 Participants |
| Sex: Female, Male Female | 62 Participants | 26 Participants | 88 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 31 / 62 | 12 / 26 |
| other Total, other adverse events | 61 / 62 | 26 / 26 |
| serious Total, serious adverse events | 12 / 62 | 7 / 26 |
Outcome results
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)
Time frame: From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 4 months)
Population: Efficacy Evaluable Analysis Set: includes all participants in the safety population who have measurable disease at baseline per RECIST v1.1 by IRC and have at least one evaluable post baseline tumor assessment by IRC unless discontinued treatment due to clinical progression or death prior to tumor assessment. Participants with available data were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TNBC | Objective Response Rate (ORR) as Assessed by Independent Radiology Review (IRC) | 38.2 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Objective Response Rate (ORR) as Assessed by Independent Radiology Review (IRC) | 61.9 Percentage of participants |
p-value: 0.021Exact Binomial Test
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
Time frame: From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months)
Population: Efficacy Evaluable Set; Participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TNBC | Clinical Benefit Rate (CBR) as Assessed by IRC and Investigator | Investigator | 41.8 Percentage of participants |
| TNBC | Clinical Benefit Rate (CBR) as Assessed by IRC and Investigator | IRC | 43.6 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Clinical Benefit Rate (CBR) as Assessed by IRC and Investigator | IRC | 71.4 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Clinical Benefit Rate (CBR) as Assessed by IRC and Investigator | Investigator | 66.7 Percentage of participants |
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 \[NE\].
Time frame: Approximately 2 years and 10 months
Population: Efficacy Evaluable Analysis Set; Participants with available data were included in the analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TNBC | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | IRC - NE | 0 Percentage of participants |
| TNBC | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | IRC - CR | 5.5 Percentage of participants |
| TNBC | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | Investigator - CR | 3.6 Percentage of participants |
| TNBC | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | IRC - SD | 34.5 Percentage of participants |
| TNBC | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | Investigator - PR | 32.7 Percentage of participants |
| TNBC | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | Investigator - PD | 27.3 Percentage of participants |
| TNBC | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | Investigator - SD | 36.4 Percentage of participants |
| TNBC | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | IRC - PD | 27.3 Percentage of participants |
| TNBC | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | Investigator - NE | 0 Percentage of participants |
| TNBC | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | IRC - PR | 32.7 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | Investigator - NE | 0 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | IRC - CR | 4.8 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | IRC - PR | 57.1 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | IRC - SD | 28.6 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | IRC - PD | 9.5 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | IRC - NE | 0 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | Investigator - CR | 0 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | Investigator - PR | 57.1 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | Investigator - PD | 19.0 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator | Investigator - SD | 23.8 Percentage of participants |
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
Time frame: From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months).
Population: Efficacy Evaluable Set; Participants with available data were included in the analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TNBC | Disease Control Rate (DCR) as Assessed by IRC and Investigator | IRC | 72.7 Percentage of participants |
| TNBC | Disease Control Rate (DCR) as Assessed by IRC and Investigator | Investigator | 72.7 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Disease Control Rate (DCR) as Assessed by IRC and Investigator | IRC | 90.5 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | Disease Control Rate (DCR) as Assessed by IRC and Investigator | Investigator | 81.0 Percentage of participants |
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
Time frame: From first documentation of confirmed CR or PR to first documentation of disease progression or death (Approximately 2 years and 10 months)
Population: Efficacy Evaluable Analysis Set; Only the participants with confirmed objective responses by IRC were included in DOR analysis;
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TNBC | Duration of Response (DOR) as Assessed by IRC | 6.97 Months |
| HR(+) /HER2(-) Breast Cancer | Duration of Response (DOR) as Assessed by IRC | 7.49 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
Time frame: From first documentation of confirmed CR or PR to first documentation of disease progression or death (Approximately 2 years and 10 months)
Population: Efficacy Evaluable Analysis Set; Only the participants with confirmed objective responses by Investigator were included in DOR analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TNBC | Duration of Response (DOR) as Assessed by the Investigator | 6.28 Months |
| HR(+) /HER2(-) Breast Cancer | Duration of Response (DOR) as Assessed by the Investigator | 11.57 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.
Time frame: Up to approximately 2 years and 10 months
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TNBC | Number of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Grade 3 or higher | 37 participants |
| TNBC | Number of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | With At Least 1 TEAE | 61 participants |
| TNBC | Number of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | SAEs | 12 participants |
| HR(+) /HER2(-) Breast Cancer | Number of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | With At Least 1 TEAE | 26 participants |
| HR(+) /HER2(-) Breast Cancer | Number of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Grade 3 or higher | 18 participants |
| HR(+) /HER2(-) Breast Cancer | Number of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | SAEs | 7 participants |
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)
Time frame: From the first dose of pamiparib to first documentation of disease progression while participant is alive (Approximately 2 years and 10 months)
Population: Efficacy Evaluable Analysis Set; Participants with available data were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TNBC | ORR as Assessed by Investigator | 36.4 Percentage of participants |
| HR(+) /HER2(-) Breast Cancer | ORR as Assessed by Investigator | 57.1 Percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as time from the first dose of pamiparib to the date of death due to any cause
Time frame: From the first dose of pamiparib until death (approximately 2 years and 10 months)
Population: Safety Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TNBC | Overall Survival (OS) | 17.08 Months |
| HR(+) /HER2(-) Breast Cancer | Overall Survival (OS) | 27.89 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
Time frame: From the first dose of pamiparib to first documentation of disease progression or death (Approximately 2 years and 10 months)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TNBC | Progression-free Survival (PFS) as Assessed by IRC and Investigator | Investigator | 3.78 Months |
| TNBC | Progression-free Survival (PFS) as Assessed by IRC and Investigator | IRC | 5.49 Months |
| HR(+) /HER2(-) Breast Cancer | Progression-free Survival (PFS) as Assessed by IRC and Investigator | IRC | 9.20 Months |
| HR(+) /HER2(-) Breast Cancer | Progression-free Survival (PFS) as Assessed by IRC and Investigator | Investigator | 9.69 Months |