Niraparib + Dostarlimab In BRCA Mutated Breast Cancer

NCT04584255 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20-371
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 8

Brief Summary

This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with BRCA and PALB2 mutations. The names of the study drugs involved in this study are:

• Niraparib (Zejula)
• Dostarlimab

Conditions

Stage I Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer; Breast Cancer; HER2-negative Breast Cancer; Germline BRCA1 Gene Mutation; Germline BRCA2 Gene Mutation; Deleterious PALB2 Gene Mutation

Keywords

Invasive Breast Cancer Stage I; Invasive Breast Cancer Stage II; Invasive Breast Cancer Stage III; Breast Cancer; HER2-negative invasive tumor

Outcome Measures

Primary Outcomes (2)

• Tumor-infiltrating lymphocytes (TILs)

  The primary evaluation of change in TILs within each arm will be based on a Wilcoxon signed rank test (absolute difference) using a one-sided alpha = 0.05 for each arm

  baseline to 21 days

• The number and proportion of participants achieving Pathologic Complete Response (pCR)

  The number and proportion of participants achieving pCR among all participants who initiate protocol therapy will be summarized with a two-sided 90% exact confidence interval.

  18 weeks

Secondary Outcomes (4)

• pCR rate (ER+/HER2- BC patients)

  18 weeks

• Changes in TILs

  baseline up to 3 weeks

• Rate of Residual Cancer Burden (RCB) 0/1 response

  18 Weeks

• Number of Participants With Treatment-Related NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  baseline up to 5 years

Study Arms (3)

Arm A Triple Negative Breast Cancer (TNBC)

EXPERIMENTAL

Participants will be randomized 1:1 to treatment with the combination (Arm A) * Niraparib-Daily beginning with week 1, day 1 * Dostarlimab-Once every three weeks beginning with week 1, day 1

Drug: Niraparib; Drug: Dostarlimab

Arm B TNBC

EXPERIMENTAL

Participants will be randomized 1:1 to treatment with the combination (Arm B) * 3-week lead-in of niraparib monotherapy followed by treatment with the combination * Niraparib Daily beginning with week 1, day 1 * Dostarlimab Once every three weeks beginning with week 4, day 1

Drug: Niraparib; Drug: Dostarlimab

Arm C ER+/HER2-

EXPERIMENTAL

exploratory cohort of estrogen receptor (ER) positive HER2-negative participants will be enrolled to Arm C. * Niraparib Daily beginning with week 1, day 1 * Dostarlimab Once every three weeks beginning with week 1, day 1

Drug: Niraparib; Drug: Dostarlimab

Interventions

Niraparib DRUG

Predetermined dosage PO Daily

Also known as: Zejula

Arm A Triple Negative Breast Cancer (TNBC); Arm B TNBC; Arm C ER+/HER2-

Dostarlimab DRUG

Predetermined Dosage, IV,q3 weeks

Also known as: TSR042

Arm A Triple Negative Breast Cancer (TNBC); Arm B TNBC; Arm C ER+/HER2-

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study. Laboratory assessments for eligibility must be completed within 14 days prior to the date of registration. Diagnostic imaging, such as MRIs and CT scans, must be performed within 28 days of the planned treatment start.
• Participants must have histologically or cytologically confirmed invasive breast cancer Stage I to III with primary tumor size at least 1.0 cm defined by physical exam or imaging (whichever is larger). In the case of a multifocal, multicentric, or bilateral disease, the largest lesion must be ≥ 1.0 cm and designated as the "index" lesion for tumor evaluations. Patients with inflammatory breast carcinoma are not eligible.
• Participants must have documentation of estrogen receptor (ER) and progesterone receptor (PR) testing by IHC according to local institutional guidelines in a CLIA-approved setting. Central confirmation of ER/PR status is not required. All tumors must be HER2 negative.
• Arms A and B: Target lesion must be ER and PR negative (\<10% staining) by local review.
• Arm C: Target lesion must be ER and/or PR positive (\>10% staining) by local review.
• Participants must have documented HER2-negative invasive tumor according to local institutional guidelines in a CLIA-approved setting. Central confirmation of HER2 status is not required. HER2 negative is defined as:
• or 1+ by IHC, OR
• Lack of gene amplification with HER2/CEP17 ratio \< 2 by ISH, OR
• Copy number \< 6 by ISH
• Participants must have documented germline mutation in BRCA1, BRCA2 or PALB2 that is deleterious or suspected to be deleterious (known or predicted to be detrimental/lead to loss of function). Mutation must be identified through a CLIA-approved laboratory. Final determination of eligibility for any discordant results in pathogenicity will be made by the sponsor-investigator. A formal eligibility exception will not be required in these cases as long as approval by overall study PI is granted and documented.
• Participants with multifocal, multicentric or bilateral disease are eligible if at least one lesion meets criteria for the study. In this circumstance, the investigator must determine which will represent the target lesion to be assessed for response. This should remain consistent throughout the study. The target lesion should be selected on the basis of its size (lesion with the longest diameter) and suitability for accurate repetitive measurements.
• Participants with an eligible target lesion, and another small HER2+ tumor (for example, \< 6 mm), may be eligible for enrollment following discussion and agreement with the overall principal investigator. A formal eligibility exception will not be required in these cases as long as approval by the sponsor-investigator is granted and documented.
• Female or male ≥ 18 years of age
• Breast imaging should include imaging of the ipsilateral axilla. For subjects with a clinically positive axilla by physical examination or imaging, axillary tissue acquisition is not required. For patients with a clinically negative axilla by examination and imaging, tissue acquisition is not required. For equivocal imaging findings, tissue acquisition (a needle aspiration, core biopsy) is required. Sentinel Lymph Node (SLN) biopsy before neoadjuvant therapy is not allowed.
• ECOG performance status of 0 or 1

You may not qualify if:

• Stage IV breast cancer.
• Concurrent therapy with any other investigational product
• Prior treatment for the current breast cancer, including prior chemotherapy, immune therapy, hormonal therapy, radiation, or investigational therapy for this diagnosis.
• Excisional biopsy of the primary tumor and/or excision of axillary lymph nodes, including SLNB, prior to study treatment.
• Participants with a history of malignancy are ineligible except in the following circumstances:
• Individuals with a history of invasive breast cancer are not eligible unless they have been disease-free for a minimum of three years.
• Individuals with a malignancy history other than invasive breast cancer are eligible if they have no active malignancy and are deemed by the investigator to be at low risk for recurrence of that malignancy.
• Individuals with the following cancer history are eligible: adequately treated nonmelanoma skin cancers, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma.
• Other exceptions may exist following agreement with the sponsor-investigator
• Patients with a diagnosis of immunodeficiency, or currently receiving systemic steroid therapy or any other form of immunosuppressive within 7 days prior to the first dose of study treatment. Use of local corticosteroid injections (e.g. intraarticular injections), inhaled, intranasal, ophthalmic, and topical corticosteroids, and subjects requiring corticosteroid pre-medication for hypersensitivity reactions (e.g. CT scan pre-medication) are allowed.
• Patients with autoimmune disease that has required systemic treatment within the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Patients with a history of interstitial lung disease or pneumonitis.
• Patients who have received a live vaccine within 2 weeks prior to the start of study treatment.
• Patients who have undergone any major surgery within 3 weeks prior to study entry, patients must have recovered to baseline from any effects of any major surgery.
• Patients with concurrent HIV infection are eligible provided they meet the following criteria:

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Translational Breast Cancer Research Consortium: collaborator
• Johns Hopkins University: collaborator
• GlaxoSmithKline: collaborator

Study Sites (8)

Yale University Cancer Center

New Haven, Connecticut, 06520, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Washington / Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

niraparib; dostarlimab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Erica L. Mayer, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 8, 2020
• First Posted: October 12, 2020
• Study Start: December 18, 2020
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 17, 2029
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (8)