MEDI4736 and Tremelimumab in Treating Patients With Metastatic HER2 Negative Breast Cancer
Condition: Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Anti-B7H1 Monoclonal Antibody MEDI4736; Laboratory Biomarker Analysis; Pharmacological Study; Tremelimumab
Intervention description: Given IV; Correlative studies; Correlative studies; Given IV
Intervention MeSH terms: Antineoplastic Agents, Immunological; Durvalumab; Ipilimumab; Tremelimumab; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of this study is to determine the anti-tumor activity of MEDI4736 in
      combination with tremelimumab in patients with metastatic HER2-negative breast cancer. Both
      MEDI4736 and tremelimumab are antibodies (proteins used by the immune system to fight
      infections and cancers). MEDI4736 attaches to a protein in tumors called PD-L1. It may
      prevent cancer growth by helping certain blood cells of the immune system get rid of the
      tumor. Tremelimumab stimulates (wakes up) the immune system to attack the tumor by inhibiting
      a protein molecule called CTLA-4 on immune cells. Combining the actions of these drugs may
      result in better treatment options for patients with breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a histologically documented (either primary or metastatic site)
             diagnosis of breast cancer that is HER2 non-overexpressing by immunohistochemistry,
             namely 0 or 1; if they have an equivocal immunohistochemistry, 2, the tumor must be
             non-gene amplified by fluorescence in situ hybridization (FISH) performed upon the
             primary tumor or metastatic lesion (ratio < 2 and HER2 copy number < 4); estrogen
             receptor (ER) positivity is defined as 1% or greater

          -  Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors
             (RECIST) criteria

          -  Patients who are ER negative must have progressed through at least one prior
             chemotherapy regimen in the metastatic setting or within 12 months of their last
             adjuvant systemic treatment; patients who are ER positive must have progressed through
             standard hormone therapy options and have received at least one line of chemotherapy
             in the metastatic setting

          -  Completion of prior chemotherapy systemic anticancer therapy at least 2 weeks prior to
             study entry

          -  Radiation therapy must be completed at least 2 weeks prior to study entry; radiated
             lesions may not serve as measurable disease unless they have been radiated over 12
             months prior to enrollment

          -  Patients may have parenchymal brain metastases if stable (no evidence of progression)
             for at least 1 month after local therapy (radiation or surgery); leptomeningeal
             disease is excluded; must have completed any prescribed steroid taper

          -  Patients may have had a prior diagnosis of cancer if it has been > 5 years since their
             last treatment

          -  Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status
             of =< 2

          -  Absolute neutrophil count >= 1,000/mcL

          -  Platelets >= 50,000/mcl

          -  Total bilirubin =< 1.5 times the institutional upper limit of normal (ULN) (or =< 3
             times ULN in case of liver metastasis)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT])
             =< 2.5 X institutional ULN (or =< 5 times ULN in case of liver metastasis)

          -  Creatinine =< 2 ng/ml

          -  Females of child-bearing potential (FOCBP) and males must agree to use 2 methods of
             adequate contraception prior to study entry, for the duration of study participation,
             and for number (#) days following completion of therapy; should a female patient
             become pregnant or suspect she is pregnant while participating in this study, she
             should inform her treating physician immediately

               -  NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a
                  tubal ligation, or remaining celibate by choice) who meets the following
                  criteria:

               -  Has not undergone a hysterectomy or bilateral oophorectomy

               -  Has had menses at any time in the preceding 12 consecutive months (and therefore
                  has not been naturally postmenopausal for > 12 months)

          -  FOCBP must have a negative pregnancy test within 7 days prior to registration on study

          -  Willingness to provide a fresh biopsy prior to study enrollment and after 2 cycles of
             treatment

          -  Patients must have the ability to understand and the willingness to sign a written
             informed consent prior to registration on study

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering
             the study or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier are not eligible.

          -  Current or prior use of immunosuppressive therapy within 2 weeks of starting
             investigational therapy

          -  Patients who are taking any herbal (alternative) medicines are NOT eligible for
             participation; patients must be off any such medications by the time of registration
             for at least 2 weeks; NOTE: Vitamin supplements are acceptable

          -  Patients may not have received any other investigational agents within 4 weeks prior
             to registration

          -  Prior treatment with immune therapy (including but not limited to cluster of
             differentiation [CD]137, OX40, programmed death [PD]-1, PD-L1 or cytotoxic
             T-lymphocyte antigen 4 [CTLA4] inhibitors)

          -  Prior severe infusion reaction to a monoclonal antibody

          -  Patients with a history of or active autoimmune disease within the past 3 years with
             the following exceptions:

               -  Vitiligo or alopecia

               -  Hypothyroidism on stable doses of thyroid replacement therapy

               -  Psoriasis not requiring systemic therapy within the past 3 years

          -  History of primary immunodeficiency disease or tuberculosis

          -  Major medical conditions that might affect study participation (uncontrolled
             pulmonary, renal, or hepatic dysfunction, uncontrolled infection) are not eligible;
             other significant comorbid condition which the investigator feels might compromise
             effective and safe participation in the study

          -  Patients who have an uncontrolled intercurrent illness including, but not limited to
             any of the following, are not eligible:

               -  Uncontrolled pulmonary, renal, or hepatic dysfunction

               -  Ongoing or active infection requiring systemic treatment

               -  Known active or chronic viral hepatitis or human immunodeficiency virus (HIV)

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

               -  Any other illness or condition that the treating investigator feels would
                  interfere with study compliance or would compromise the patient's safety or study
                  endpoints

          -  Female patients who are pregnant or nursing are not eligible