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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 | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE3

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

A Randomized Phase 3 Double-Blinded Study Comparing the Efficacy and Safety of Niraparib to Placebo in Participants With Either HER2-Negative BRCA-Mutated or Triple-Negative Breast Cancer With Molecular Disease Based on Presence of Circulating Tumor DNA After Definitive Therapy (ZEST)

NCT04915755•GlaxoSmithKline

View on ClinicalTrials.gov

Summary

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.

Eligibility

Age

18 - No limit years

Sex

ALL

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.
+1 more criteria

Locations (198)

GSK Investigational Site

Burbank, California, United States

GSK Investigational Site

Duarte, California, United States

GSK Investigational Site

Palo Alto, California, United States

GSK Investigational Site

San Francisco, California, United States

GSK Investigational Site

Aurora, Colorado, United States

GSK Investigational Site

Highlands Ranch, Colorado, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Skokie, Illinois, United States

GSK Investigational Site

Ann Arbor, Michigan, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

Key Dates

Start Date

June 28, 2021

Primary Completion Date

June 28, 2024

Completion Date

December 31, 2025

Last Updated

July 16, 2025

Enrollment

ACTUAL participants

Conditions

Neoplasms, Breast

Interventions

Niraparib

DRUG

Placebo

DRUG

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UNKNOWNNA

Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: July 16, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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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

Inclusion Criteria

Exclusion Criteria

ALTTO (Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation) Study; BIG 2-06/N063D

ErbB2 Over-expressing Metastatic Breast Cancer Study Using Paclitaxel, Trastuzumab, and Lapatinib

Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA

GW572016 With Docetaxel and Trastuzumab for the Treatment Of Untreated ErbB2 Over-Expressing Metastatic Breast Cancer

A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients

Pre- Versus Postoperative Accelerated Partial Breast Irradiation