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 (ZEST)

GlaxoSmithKline (GSK)

Status and phase: Active, not recruiting; Phase 3

Conditions: Neoplasms, Breast

Treatments: Drug: Placebo; Drug: Niraparib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04915755

213831

2020-003973-23 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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43 participants in 2 patient groups

Cohort1:Participants with tBRCAmut HER2-breast cancer(Independent of HR status,including HR+andTNBC)

Experimental group

Description:

Eligible participants will receive either Niraparib or Placebo.

Treatment:

Drug: Niraparib

Drug: Placebo

Cohort 2: Participants with tBRCAwt TNBC

Experimental group

Description:

Eligible participants will receive either Niraparib or Placebo.

Treatment:

Drug: Niraparib

Drug: Placebo