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Age ≥ 18 years |
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ECOG performance status ≤ 1 |
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Histologically or cytologically-confirmed TNBC (ER <1%, PR <1%, HER-2-neu 0-1+ by IHC or non-FISH-amplified63. ER-low, PR-low (defined as ER and/or PR 1-10%) and HER2-negative patients may also be eligible, as per treating MD discretion) |
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Metastatic or recurrent TNBC |
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Prior progression on immune-checkpoint inhibitor and/or PDL1-negative. Note: PDL1-status may be determined on tissues from either primary or mTNBC. PD-L1 status must be determined by an FDA-approved assay approved for breast cancer, such as PharmDx IHC (22C3) for pembrolizumab, Ventana (SP142) for atezolizumab |
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No more than 2 prior lines of systemic therapy for inoperable/recurrent or metastatic disease |
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Note: Prior line of systemic therapy includes targeted or biologic agents in combination or |
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the absence of chemotherapy |
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Radiation is clinically indicated for local control or palliation |
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At least one tumor for which RT is considered clinically appropriate |
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At least one radiographically-confirmed metastases index lesion that will not undergo |
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Prior therapy with targeted agents or other forms of immunotherapy is allowed |
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RT and is measurable based on RECIST v1.1 |
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Prior RT is permitted, provided the treating radiation oncologist deems that study RT |
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treatment planning guidelines can be achieved |
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Hematology |
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Available archived tumor tissue of a metastatic tumor collected up to 28 days prior to |
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registration. If archival tissue is unavailable, participant willingness to provide |
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tissue from a newly obtained core or excisional biopsy of a tumor lesion |
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Newly-obtained is defined as a specimen obtained up to 28 days prior to study |
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Renal Function |
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registration |
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Adequate organ function (assessed within 8 days prior to initiation of protocol |
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treatment, unless otherwise indicated) as follows |
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Hepatic Function |
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Absolute Neutrophil Count (ANC) ≥1500/mm3 |
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Platelet Count ≥100,000/mm3 |
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Hemoglobin ≥9.0 g/dL |
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Serum Creatinine ≤ 1.5 x upper limit of normal (ULN) or |
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Creatinine clearance should be calculated per institutional standard |
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Measured or calculated a creatinine clearance ≥ 60 mL/min for participant |
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with (GFR can also be used in place of creatinine creatinine levels > 1.5 X |
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ULN or CrCl |
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Total Bilirubin ≤ 1.5 mg/dL (Direct bilirubin ≤ ULN for participants with |
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total bilirubin levels > 1.5 ULN) |
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INR, PT, aPTT ≤ 1.5 x ULN (participants receiving anticoagulant therapy must |
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have PT or PTT within therapeutic range) |
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Albumin ≥ 2.5 mg/dL |
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Aspartate Aminotransferase (AST) ≤ 2.5 x ULNb |
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Alanine Aminotransferase (ALT) ≤ 2.5 x ULNb ULN = upper normal limit of |
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institution's normal range |
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Participants with liver metastases may have AST and/or ALT ≤ 5 x ULN |
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Female participant has a negative urine or serum pregnancy test within 7 days prior to |
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Ability to swallow (whole) and retain oral medications |
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study treatment if a woman has child-bearing potential and agrees to abstain from |
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Ability to understand and the willingness to sign a written informed consent document |
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activities that could result in pregnancy from screening through 180 days after the |
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last dose of study treatment or is of non-childbearing potential |
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Non-childbearing potential is defined as follows (by other than medical reasons) |
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≥45 years of age and has not had menses for >1 year |
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Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and |
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oophorectomy must have a follicle stimulating hormone value in the postmenopausal |
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range upon screening evaluation |
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Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented |
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hysterectomy or oophorectomy must be confirmed with medical records of the actual |
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procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical |
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records of the actual procedure |
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Women of childbearing potential should be willing to use 2 methods of birth |
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control or be surgically sterile, or abstain from heterosexual activity for the |
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course of the study through 180 days after the last dose of study medication |
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Participants of childbearing potential are those who have not been surgically |
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sterilized or have not been free from menses for > 1 year |
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Note: Abstinence is acceptable if this is the established and preferred contraception for |
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the patient |
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Male participant agrees to use an adequate method of contraception starting with the |
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first dose of study treatment through 90 days after the last dose of study treatment |
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Note: Abstinence is acceptable if this is the established and preferred contraception |
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for the patient |
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Male subjects must not donate sperm starting with the first dose of study drug through |
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days after the last dose of study drug |
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Participant must agree not to breastfeed during the study or for 30 days after the |
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last dose of study treatment |
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Participant must agree to not donate blood during the study or for 90 days after the |
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last dose of study treatment |
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Participants who meet any of the following criteria will be excluded
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Known germline or somatic BRCA mutation-positive status
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Hypersensitivity to niraparib or dostarlimab components or its excipients
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Active infection requiring systemic therapy
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Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
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Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
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Known history of active TB (Bacillus Tuberculosis)
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Known active brain metastases or LMD (leptomeningeal disease). Note: Patients with
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previously treated brain metastases may participate provided they are stable (without
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evidence of progression by imaging [using the identical imaging modality for each
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assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of
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study treatment and any neurologic symptoms have returned to baseline), have no
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evidence of new or enlarging brain metastases, and have not been using steroids for at
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least 7 days prior to study treatment
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Known additional malignancy that progressed or required treatment in the last 2 years
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Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
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skin that has undergone potentially curative therapy or in situ cervical cancer
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Prior treatment with either a PARP inhibitor or ICI is permitted, however, prior
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receipt of both therapies is excluded
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Receipt of >2 lines of chemo in the metastatic setting (including targeted or biologic
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agents in combination or the absence of chemotherapy)
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Participation in a study of an investigational agent and received study therapy or
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used an investigational device within 4 weeks (or at least 5 half-lives from previous
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therapy) of the first dose of study treatment
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Receipt of prior cytotoxic therapy or targeted small molecule therapy within 2 weeks
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prior to study Day 1 or who has not recovered (i.e., > Grade 1 or at baseline) from
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adverse events due to a previously administered agent, including grade 2 alopecia
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Note: Participants with ≤ Grade 2 neuropathy are an exception to this criterion and may
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qualify for the study
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Patients who have undergone any major surgery within 3 weeks prior to study entry
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patients must have recovered adequately from the toxicity and/or complications from
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the intervention prior to starting therapy
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Active autoimmune disease that has required systemic treatment in the past 2 years
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(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
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drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
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replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
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form of systemic treatment
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Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
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form of immunosuppressive therapy within 7 days prior to the first dose of trial
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treatment. Use of local corticosteroid injections (e.g. intra-articular injections)
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inhaled, intranasal, ophthalmic, and topical corticosteroids, and subjects requiring
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corticosteroid pre-medication for hypersensitivity reactions (e.g. CT scan
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pre-medication) are allowed
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Known history of/active, non-infectious pneumonitis requiring treatment with steroids
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or has history of/active interstitial lung disease
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History or current evidence of any condition, therapy, or laboratory abnormality that
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might confound the results of the trial, interfere with the patient's participation
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for the full duration of the trial, or is not in the best interest of the patient to
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participate, in the opinion of the treating investigator
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Known psychiatric or substance abuse disorders that would interfere with cooperation
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with the requirements of the trial
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Participant has a serious, uncontrolled medical disorder, nonmalignant systemic
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disease, or active, uncontrolled infection. Examples include, but are not limited to
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uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction
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uncontrolled major seizure disorder, unstable spinal cord compression
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Pregnant or breastfeeding or expecting to conceive or father children within the projected
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duration of the trial, starting with the pre-screening or screening visit through 180 days
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after the last dose of trial treatment
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Known active Hepatitis B (e.g., HbsAg reactive) or Hepatitis C (e.g., HCV RNA
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[qualitative] is detected)
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Receipt of a live vaccine within 14 days of planned start of study therapy. Note
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Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
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are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
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attenuated vaccines, and are not allowed
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Participant must not have received a transfusion (platelets or red blood cells) ≤ 4
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weeks prior to initiating protocol therapy
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Participant must not have received colony stimulating factors (eg, granulocyte
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colony-stimulating factor, granulocyte macrophage colony stimulating factor, or
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recombinant erythropoietin) within 4 weeks prior initiating protocol therapy
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Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due
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to prior chemotherapy that persisted > 4 weeks and was related to the most recent
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treatment
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Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the
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exception of non-clinically significant lab abnormalities
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