A Study of Pembrolizumab and Ruxolitinib Phosphate for Treating Patients with Metastatic Stage IV Triple Negative Breast Cancer


About this study

The purpose of this study is to assess the side effects and best dose of ruxolitinib phosphate when given together with pembrolizumab for treating patients with stage IV triple negative breast cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Ruxolitinib phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and ruxolitinib phosphate together may work better in treating patients with stage IV triple negative breast cancer.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Age ≥ 18 years old.
  • Metastatic (stage IV) triple negative breast cancer that has progressed after at least one prior chemotherapy regimen in the metastatic setting or refusal of chemotherapy in the metastatic setting.  Non-measurable disease (i.e., bone metastases) is permitted.
  • Histological confirmation of triple negative breast cancer defined as:
    • Her2/neu by FISH (ratio ≤ 1.8) or IHC (0 or 1+);
    • ER and PR expression < 10%.
  • The following laboratory values obtained  ≤ 7 days prior to registration:
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
    • Platelet count ≥ 100,000/mm^3;
    • Total bilirubin ≤ 1.5 x Upper Limit Normal (ULN);
    • AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or < 5 x ULN if organ involvement;
    • Alkaline Phosphatase < 5 x ULN;
    • Serum creatinine ≤ 2 x ULN or 24 hour Cr clearance > 60ml/min.
  • ECOG Performance Status (PS) 0 or 1.
  • Ability to provide informed written consent and be able to adhere to the study visit schedule and other protocol requirements.
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
  • Willing to provide blood samples for correlative research purposes.
  • Has existing archived tissue and is willing to consent to providing sample for correlative research purposes.          
  • Female subjects of childbearing potential should have a negative serum pregnancy ≤ 7 days prior to registration.     
  • 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.
    • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
    • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Radiographic or clinically measurable evidence of disease progression.
  • Prior therapy with atezolizumab is acceptable providing that all atezolizumab-related toxicities have resolved.

Exclusion Criteria:

  • Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection,  known positive for active infectious hepatitis, type A, B or C (past infection allowed), or psychiatric illness/social situations that would limit compliance with study requirements.
    • Note: ongoing infection controlled on antibiotics/antifungal/antiviral medications are allowed
  • Any of the following prior therapies:
    • Cytotoxic Chemotherapy  ≤ 14 days prior to registration;
    • Immunotherapy  ≤ 14 days prior to registration;
    • Biologic therapy (i.e., antibody therapies) ≤ 28 days prior to registration;
    • Radiation therapy  ≤ 14 days prior to registration;
    • Targeted therapies (i.e., PARP inhibitors, ≤ 7 days or 5 half-lives whichever is shorter);
    • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm ≤ 14 days prior to registration.
  • Active uncontrolled CNS metastases.
  • Immunocompromised patients and patients known to be HIV positive.
  • Hypersensitivity to Ruxolitinib or any of its excipients.
  • Major surgery ≤ 28 days prior to registration.
    • Note:  If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Clinically significant heart disease, including the following:
    • Active severe angina pectoris prior to registration;
    • Acute myocardial infarction prior to registration;
    • New York Heart Association classification IV cardiovascular disease or symptomatic class III disease.
      • Note: patients with any of the above may be allowed after discussion amongst the investigators including the principal investigator
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Registration.
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) ≤4 weeks prior to registration or who has not recovered (i.e., ≤ Grade 1 or at baseline level) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy  who has not recovered (i.e., ≤ Grade 1 or at baseline level) from adverse events due to a previously administered agent.
    • Note:  Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Has a known additional malignancy that is progressing or requires active treatment.  Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has 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). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • 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. 
  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
    • Men or women of childbearing potential who are unwilling to employ adequate contraception;
    • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with pembrolizumab, nivolumab, avelumab, durvalumab.
  • Has received a live vaccine within 30 days of planned start of registration.
    • Note:  Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Evidence of pericardial involvement with metastatic breast cancer (effusion, pericardial thickening).
  • Radiographic evidence of pulmonary lymphangitic spread of metastatic breast cancer.
  • Evidence of bilateral pleural involvement with metastatic breast cancer (effusions, pleural thickening).
  • Elevated serum lactate dehydrogenase level (LDH > laboratory ULN) associated with any clinical or radiographic evidence of intrathoracic metastatic breast cancer.








Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Donald Northfelt, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


Publications are currently not available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

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