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NCT03575065

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

Completed Phase 2 Results posted Last updated 26 October 2024
What this trial tests

Phase 2 trial testing BGB-290 in HER2-negative Breast Cancer in 88 participants. Completed in 14 April 2021.

Timeline
22 June 2018
Primary endpoint
9 October 2020
14 April 2021

Quick facts

Lead sponsorBeiGene
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment88
Start date22 June 2018
Primary completion9 October 2020
Estimated completion14 April 2021
Sites20 locations across China

Drugs / interventions tested

Conditions studied

Sponsor

BeiGene — full company profile →

Who can join

18 and older, any sex, with HER2-negative Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) as Assessed by Independent Radiology Review (IRC) Primary · 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)

GroupValue95% CI
TNBC38.225.4 – 52.3
HR(+) /HER2(-) Breast Cancer61.938.4 – 81.9
ORR as Assessed by Investigator Secondary · 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)

GroupValue95% CI
TNBC36.423.8 – 50.4
HR(+) /HER2(-) Breast Cancer57.134.0 – 78.2
Progression-free Survival (PFS) as Assessed by IRC and Investigator Secondary · 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

IRC
GroupValue95% CI
TNBC5.493.65 – 7.33
HR(+) /HER2(-) Breast Cancer9.207.39 – 11.93
Investigator
GroupValue95% CI
TNBC3.783.68 – 6.41
HR(+) /HER2(-) Breast Cancer9.695.55 – 12.85
Duration of Response (DOR) as Assessed by IRC Secondary · 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

GroupValue95% CI
TNBC6.973.94 – NA
HR(+) /HER2(-) Breast Cancer7.495.55 – 14.75
Duration of Response (DOR) as Assessed by the Investigator Secondary · 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

GroupValue95% CI
TNBC6.284.63 – 11.76
HR(+) /HER2(-) Breast Cancer11.575.95 – 13.90
Confirmed Best Overall Response (BOR) as Assessed by IRC and Investigator Secondary · 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 \[NE\].

IRC - CR
GroupValue95% CI
TNBC5.5
HR(+) /HER2(-) Breast Cancer4.8
IRC - PR
GroupValue95% CI
TNBC32.7
HR(+) /HER2(-) Breast Cancer57.1
IRC - SD
GroupValue95% CI
TNBC34.5
HR(+) /HER2(-) Breast Cancer28.6
IRC - PD
GroupValue95% CI
TNBC27.3
HR(+) /HER2(-) Breast Cancer9.5
IRC - NE
GroupValue95% CI
TNBC0
HR(+) /HER2(-) Breast Cancer0
Investigator - CR
GroupValue95% CI
TNBC3.6
HR(+) /HER2(-) Breast Cancer0
Investigator - PR
GroupValue95% CI
TNBC32.7
HR(+) /HER2(-) Breast Cancer57.1
Investigator - SD
GroupValue95% CI
TNBC36.4
HR(+) /HER2(-) Breast Cancer23.8
Disease Control Rate (DCR) as Assessed by IRC and Investigator Secondary · 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

IRC
GroupValue95% CI
TNBC72.759.0 – 83.9
HR(+) /HER2(-) Breast Cancer90.569.6 – 98.8
Investigator
GroupValue95% CI
TNBC72.759.0 – 83.9
HR(+) /HER2(-) Breast Cancer81.058.1 – 94.6
Clinical Benefit Rate (CBR) as Assessed by IRC and Investigator Secondary · 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

IRC
GroupValue95% CI
TNBC43.630.3 – 57.7
HR(+) /HER2(-) Breast Cancer71.447.8 – 88.7
Investigator
GroupValue95% CI
TNBC41.828.7 – 55.9
HR(+) /HER2(-) Breast Cancer66.743.0 – 85.4
Overall Survival (OS) Secondary · 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

GroupValue95% CI
TNBC17.0815.57 – NA
HR(+) /HER2(-) Breast Cancer27.8918.10 – NA
Number of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) Secondary · 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.

With At Least 1 TEAE
GroupValue95% CI
TNBC61
HR(+) / HER2(-) Breast Cancer26
Grade 3 or higher
GroupValue95% CI
TNBC37
HR(+) / HER2(-) Breast Cancer18
SAEs
GroupValue95% CI
TNBC12
HR(+) / HER2(-) Breast Cancer7

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 2 years and 10 months. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TNBC
Serious: 12/62 (19%)
Deaths: 31/62
HR(+)/HER2(-)
Serious: 7/26 (27%)
Deaths: 12/26

Serious adverse events (18 terms)

ReactionSystemTNBCHR(+)/HER2(-)
AnaemiaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
CataractEye disorders
DiarrhoeaGastrointestinal disorders
DeathGeneral disorders
Upper respiratory tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
Spinal meningioma benignNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Altered state of consciousnessNervous system disorders
Cerebral haemorrhageNervous system disorders
Acute kidney injuryRenal and urinary disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Other adverse events (110 terms — click to expand)

ReactionSystemTNBCHR(+)/HER2(-)
AnaemiaBlood and lymphatic system disorders
White blood cell count decreasedInvestigations
Neutrophil count decreasedInvestigations
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
VomitingGastrointestinal disorders
Platelet count decreasedInvestigations
Alanine aminotransferase increasedInvestigations
MalaiseGeneral disorders
Weight decreasedInvestigations
DiarrhoeaGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
AstheniaGeneral disorders
LeukopeniaBlood and lymphatic system disorders
Blood bilirubin increasedInvestigations
Abdominal distensionGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
Blood alkaline phosphatase increasedInvestigations
Lymphocyte count decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
InsomniaPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
FatigueGeneral disorders
NasopharyngitisInfections and infestations
HyperglycaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
PyrexiaGeneral disorders
Blood bilirubin unconjugated increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
PruritusSkin and subcutaneous tissue disorders
LymphopeniaBlood and lymphatic system disorders
Sinus tachycardiaCardiac disorders
Abdominal discomfortGastrointestinal disorders
Urinary tract infectionInfections and infestations

Most-reported serious reactions: Anaemia, Leukopenia, Febrile neutropenia, Neutropenia, Thrombocytopenia, Cataract, Diarrhoea, Death.

Data from ClinicalTrials.gov NCT03575065 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting Breast Cancer: An Overlook on Current Strategies.
    Iacopetta D, Ceramella J, Baldino N, Sinicropi MS, et al · · 2023 · cited 57× · PMID 36835056 · DOI 10.3390/ijms24043643
  2. PARP inhibitors as single agents and in combination therapy: the most promising treatment strategies in clinical trials for BRCA-mutant ovarian and triple-negative breast cancers.
    Luo L, Keyomarsi K. · · 2022 · cited 56× · PMID 35435784 · DOI 10.1080/13543784.2022.2067527
  3. BRCA-mutated breast cancer: the unmet need, challenges and therapeutic benefits of genetic testing.
    Arun B, Couch FJ, Abraham J, Tung N, et al · · 2024 · cited 46× · PMID 39215191 · DOI 10.1038/s41416-024-02827-z
  4. Pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutations: a phase II study.
    Xu B, Sun T, Shi Y, Cui J, et al · · 2023 · cited 24× · PMID 36459284 · DOI 10.1007/s10549-022-06785-z
  5. Small molecule agents for triple negative breast cancer: Current status and future prospects.
    Ou Y, Wang M, Xu Q, Sun B, et al · · 2024 · cited 15× · PMID 38290250 · DOI 10.1016/j.tranon.2024.101893
  6. Phase 1b study to assess the safety, tolerability, and clinical activity of pamiparib in combination with temozolomide in patients with locally advanced or metastatic solid tumors.
    Stradella A, Johnson M, Goel S, Park H, et al · · 2024 · cited 7× · PMID 38970256 · DOI 10.1002/cam4.7385
  7. PARP inhibitors and breast cancer: from therapeutic breakthrough to resistance challenge.
    Wang W, Cai C, Qin S, He L, et al · · 2026 · PMID 41963466 · DOI 10.1038/s12276-026-01673-8
  8. Recent Advances in Drug Discovery for Triple-Negative Breast Cancer Treatment
    Masci D, Naro C, Puxeddu M, Urbani A, et al · · 2023

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Other trials of BGB-290

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Trials by the same sponsor.

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