Efficacy and Safety Comparison of Niraparib to Placebo in Participants With Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease

Phase 3Active Not RecruitingNCT04915755

GlaxoSmithKline40 enrolled

Overview

This study will assess the efficacy and safety of Niraparib in participants with either tumor mutation in the BRCA gene (tBRCAmut) HER2- breast cancer (Independent of hormone receptor \[HR\] status, including HR positive \[+\] and TNBC) or tumor BRCA wild type (tBRCAwt) TNBC with molecular disease based on the presence of circulating tumor Deoxyribonucleic acid (ctDNA) following surgery or completion of adjuvant therapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Neoplasms, Breast

Interventions

NiraparibDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Stage I to III breast cancer with surgical resection of the primary tumor that is confirmed to be either: TNBC, irrespective of BRCA status or HR+/HER2- breast cancer with a known and documented deleterious or suspected deleterious tBRCA mutation. * Estrogen receptor (ER) and/or progesterone receptor (PgR) negativity is defined as immunohistochemistry (IHC) nuclear staining less than (\<) 1 percentage (%), or by Allred scoring system where TNBC is defined to be 0 out of 8 or 2 out of 8, or staining in \<1 % of cancer cells. * Completed prior standard therapy for curative intent. * Participants with HR+ breast cancer must be on a stable regimen of endocrine therapy. * Detectable ctDNA as measured by central testing. * An archival tumor tissue specimen of the primary tumor sufficient in quality and quantity for ctDNA assay design and tBRCA and Homologous recombination deficiency (HRD) testing is required. * An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Exclusion Criteria: * Prior treatment with a Poly Adenosine-diphosphate Ribose Polymerase (PARP) inhibitor. * Current treatment with a Cyclin-dependent kinase (CDK)4/6 inhibitor or endocrine therapy other than anastrozole, letrozole, exemestane, and tamoxifen with or without ovarian suppression. * Participants have any sign of metastasis or local recurrence after comprehensive assessment conducted per protocol. * Participants have shown no definitive response to preoperative chemotherapy by pathologic, radiographic or clinical evaluation, in cases where preoperative chemotherapy was administered. * Participants have inadequately treated or controlled hypertension. * Participants have received live vaccine within 30 days of planned start of study randomization. * Participants have a second primary malignancy. * Exceptions are the following: (a) Adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal carcinoma in situ (DCIS) of the breast, Stage I Grade 1 endometrial carcinoma. (b) Other solid tumors and lymphomas (without bone marrow involvement) diagnosed \>=5 years prior to randomization and treated with no evidence of disease recurrence and for whom no more than 1 line of chemotherapy was applied. * Participant is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and/or for up to 180 days after the last dose of study treatment (except France). * Participant is immunocompromised. Participants with splenectomy are allowed. Participants with known human immunodeficiency virus (HIV) are allowed if they meet protocol-defined criteria. * Participants have a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Adverse Event (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, is life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, is a congenital anomaly/birth defect, other situations and is associated with liver injury or impaired liver function. SAEs are subsets of AEs. TEAE is an event that emerged during treatment having been absent pretreatment or worsened relative to the pretreatment state. AESI is any AE (serious or nonserious) that is of scientific and medical concern specific to niraparib for which ongoing monitoring and rapid communication by the Investigator to the Sponsor is warranted. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.