Niraparib + Dostarlimab In BRCA Mutated Breast Cancer

Running, not enrolling · Phase 2

Conditions studied: 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

In brief

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

Key facts

Study ID

NCT04584255

Run by

Dana-Farber Cancer Institute

People needed

62

Starts

2020-12-18

Expected to finish

2029-07-17

Last updated by the study team

2026-05-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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:
• 0 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
• Adequate organ and bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9 g/dl
• Total serum bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), (≤2.0 in patients with documented Gilbert's Syndrome)
• AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional ULN
• Serum or plasma creatinine ≤ 1.5 × institutional ULN, OR calculated creatinine clearance > 50 mL/min using the Cockcroft-Gault equation
• International normalized ratio (INR) OR prothrombin time (PT) ≤1.5× ULN. Participants who are receiving anticoagulant therapy are eligible as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) must be ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Premenopausal women must have a negative urine or serum pregnancy test within 7 days of treatment start. Women are considered non-childbearing (by other than medical reasons) if they:
• are ≥45 years of age and without menses for >1 year

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:
• CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
• No history of AIDS-defining opportunistic infection within 12 months prior to enrollment
• Any medication used in an antiretroviral therapy (ART) regimen must have no known interaction with the study agents
• Patients with active or chronic Hepatitis B or C are eligible provided they meet the liver function laboratory criteria described in 3.1.10 and cannot be on any medication with a known interaction with the study agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome or psychiatric illness/social situations that would limit compliance with study requirements.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to niraparib, dostarlimab, or their excipients.
• Transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
• Known history of myelodysplastic syndrome (MDS) or or acute myeloid leukemia (AML).

Where it is running

• Yale University Cancer Center — New Haven, Connecticut, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Vanderbilt-Ingram Cancer Center — Nashville, Tennessee, United States
• University of Washington / Fred Hutchinson Cancer Center — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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