Clinical Trials /

MEDI4736 and Tremelimumab in Treating Patients With Metastatic HER2 Negative Breast Cancer

NCT02536794

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

MEDI4736 and <span class="go-doc-concept go-doc-intervention">Tremelimumab</span> in Treating Patients With Metastatic <span class="go-doc-concept go-doc-biomarker">HER2</span> Negative <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: MEDI4736 and Tremelimumab in Treating Patients With Metastatic HER2 Negative Breast Cancer
  • Official Title: A Single Arm Phase II Study Evaluating the Efficacy and Safety of MEDI4736 in Combination With Tremelimumab in Patients With Metastatic Her2 Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02536794

    ORG ID: NU 15B01

    NCI ID: NCI-2015-01445

    Trial Conditions

    Estrogen Receptor Negative

    Estrogen Receptor Positive

    HER2/Neu Negative

    Recurrent Breast Carcinoma

    Stage IV Breast Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    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.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To evaluate clinical benefit rate in patients with metastatic HER2 negative breast cancer
    treated with MEDI4736 in combination with tremelimumab.

    SECONDARY OBJECTIVES:

    I. To evaluate progression free survival (PFS) and overall survival (OS) in patients with
    metastatic HER2 negative breast cancer treated with MEDI4736 in combination with
    tremelimumab.

    II. To evaluate safety and tolerability.

    TERTIARY OBJECTIVES:

    I. To evaluate if tissue-based immunohistochemical expression of programmed death-ligand
    (PD-L)1; tumor infiltrating lymphocytes (TILs); peripheral T cell subpopulations; changes in
    tissue and peripheral T cell receptor genotype; human leukocyte antigen (HLA) genotype; and
    immune-related candidate gene signatures predict response to MEDI4736 in combination with
    tremelimumab.

    II. To demonstrate the pharmacodynamic effects of MEDI4736 and tremelimumab on tissue and
    serum based biomarkers including PD-L1, TILs, T cell subpopulations, and T cell receptor
    genotype.

    OUTLINE:

    Patients receive MEDI4736 intravenously (IV) over 1 hour and tremelimumab IV over 1 hour on
    day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression
    or unacceptable toxicity. Four weeks after the last combination dose, patients continue to
    receive MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease
    progression or unacceptable toxicity. Patients who achieve clinical benefit (complete
    response [CR], partial response [PR], or stable disease [SD]) until the end of the 52 week
    period will then enter follow-up. During follow-up patients who develop PD may be re-treated
    with MEDI4736 at the dose previously administered IV for an additional 52 weeks using the
    same guidelines as with the initial 52 week period if they meet treatment in the setting of
    PD criteria. Only one 52 week retreatment period will be allowed.

    After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months, and
    then every 6 months for 3 years.

    Trial Arms

    Name Type Description Interventions
    Treatment (MEDI4736, tremelimumab) Experimental Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Response rate of MEDI4736 in combination with Tremelimumab

    Secondary Outcome Measures

    Toxicity of MEDI4736 in combination with Tremelimumab

    Overall Survival (OS)

    Progression Free Survival (PFS)

    Trial Keywords