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Triage: High /protocolSection/eligibilityModule/eligibilityCriteria Matched rules
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eligibility_criteria_changeEligibility criteria changes can alter the studied population.
Before
<p>Inclusion Criteria:</p><ul><li>Be willing and able to provide written informed consent/assent for the trial</li><li>Be ≥18 years of age on day of signing informed consent</li><li>Advanced BRCA-mutated breast cancer progressing on or after prior therapy for metastatic disease or locally advanced disease; Prior therapy is defined as follows: for triple negative breast cancer - progressing after at least 1 line of any prior chemotherapy; for HER2 positive disease must have progressed after at least two HER2 directed therapies in the metastatic setting including ado-trastuzumab emtansine (T-DM1); for hormone receptor positive disease (ER, PR, or both) must have progressed after palbociclib plus hormonal therapy</li><li>Measurable disease by RECIST 1.1. Patients with non-measurable bone metastases in addition to measurable disease are eligible; however patients with non-measurable bone disease as the only site(s) of disease are not eligible.</li><li>ECOG 0, 1, or 2</li><li>Documented BRCA deleterious germline mutation. (While somatic mutations in BRCA 1 and 2 do occur, there is no standardized test for this biomarker, and subjects will be limited to germline carriers).</li><li>FFPE tumor tissue available for analysis</li><li>Adequate organ function</li><li>Female subject of childbearing potential should have a negative urine or serum pregnancy prior to study registration and re-tested within 72 hours prior to receiving the first dose of pembrolizumab. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.</li><li>Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.</li><li>Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of pembrolizumab.</li></ul><p>Exclusion Criteria:</p><ul><li><p>Is currently participating or has participated in a study of investigational agent or using an investigational device with 30 days of the first dose of pembrolizumab.</p><ol><li>Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.</li><li>Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.</li><li>If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.</li></ol></li><li>Is receiving systemic steroid therapy within three days prior to the first dose of pembrolizumab or receiving any other form of immunosuppressive medication</li><li><p>Is expected to require any other form of systemic or localized antineoplastic therapy while on trial.</p><ol><li>Subjects with ER+/PR+ disease may be given endocrine therapy.</li><li>Subjects with HER2+ disease will be required to discontinue trastuzumab (Herceptin).</li></ol></li><li><p>Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Has participated in another MK03475 trial.</p><p>a. Note: Patients with or without prior PARP-inhibitor exposure may be included.</p></li><li>Has known hypersensitivity to pembrolizumab or any of its excipients</li><li>Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.</li><li>Has known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.</li><li>Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI for at least four weeks prior to the first dose of pembrolizumab and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are using no steroids for at least three days prior to study medication.</li><li>Has evidence of interstitial lung disease or active, non-infectious pneumonitis</li><li>Has active tuberculosis</li><li>Has received a live vaccine within 30 days prior to the first dose of pembrolizumab. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.</li><li>Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).</li><li>Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).</li><li>Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects that require inhaled steroid or local steroid injections will not be excluded from the study. Subjects with hypothyroidism not from autoimmune disease and stable on hormone replacement will not be excluded from the study. Note: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.</li><li>Has had an allogenic tissue / solid organ transplant.</li><li>Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.</li><li>Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.</li><li>Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit (Visit 1) through 120 days after the last dose of pembrolizumab.</li></ul>
After
<p>Inclusion Criteria:</p><ul><li>Be willing and able to provide written informed consent/assent for the trial</li><li>Be ≥18 years of age on day of signing informed consent</li><li>Advanced BRCA-mutated breast cancer progressing on or after prior therapy for metastatic disease or locally advanced disease; Prior therapy is defined as follows: for triple negative breast cancer - progressing after at least 1 line of any prior chemotherapy; for HER2 positive disease must have progressed after at least two HER2 directed therapies in the metastatic setting including ado-trastuzumab emtansine (T-DM1); for hormone receptor positive disease (ER, PR, or both) must have progressed after palbociclib plus hormonal therapy</li><li>Measurable disease by RECIST 1.1. Patients with non-measurable bone metastases in addition to measurable disease are eligible; however patients with non-measurable bone disease as the only site(s) of disease are not eligible.</li><li>ECOG 0, 1, or 2</li><li>Documented BRCA deleterious germline or somatic mutation.</li><li>FFPE tumor tissue available for analysis</li><li>Adequate organ function</li><li>Female subject of childbearing potential should have a negative urine or serum pregnancy prior to study registration and re-tested within 72 hours prior to receiving the first dose of pembrolizumab. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.</li><li>Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.</li><li>Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of pembrolizumab.</li></ul><p>Exclusion Criteria:</p><ul><li><p>Is currently participating or has participated in a study of investigational agent or using an investigational device with 30 days of the first dose of pembrolizumab.</p><ol><li>Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study Day 1.</li><li>Subjects must have recovered (i.e., ≤ Grade 1 or at baseline) from any adverse events due to a previously administered agent. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.</li><li>If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.</li></ol></li><li>Is receiving systemic steroid therapy within three days prior to the first dose of pembrolizumab or receiving any other form of immunosuppressive medication</li><li><p>Is expected to require any other form of systemic or localized antineoplastic therapy while on trial.</p><ol><li>Subjects with ER+/PR+ disease may be given endocrine therapy.</li><li>Subjects with HER2+ disease will be required to discontinue trastuzumab (Herceptin).</li></ol></li><li><p>Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Has participated in another MK03475 trial.</p><p>a. Note: Patients with or without prior PARP-inhibitor exposure may be included.</p></li><li>Has known hypersensitivity to pembrolizumab or any of its excipients</li><li>Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.</li><li>Has known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.</li><li>Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI for at least four weeks prior to the first dose of pembrolizumab and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are using no steroids for at least three days prior to study medication.</li><li>Has evidence of interstitial lung disease or active, non-infectious pneumonitis</li><li>Has active tuberculosis</li><li>Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of pembrolizumab. Administration of killed vaccines is allowed.</li><li>Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).</li><li>Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).</li><li>Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects that require inhaled steroid or local steroid injections will not be excluded from the study. Subjects with hypothyroidism not from autoimmune disease and stable on hormone replacement will not be excluded from the study. Note: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.</li><li>Has had an allogenic tissue / solid organ transplant.</li><li>Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.</li><li>Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.</li><li>Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit (Visit 1) through 120 days after the last dose of pembrolizumab.</li></ul>