Avelumab With Binimetinib, Sacituzumab Govitecan, or Liposomal Doxorubicin in Treating Stage IV or Unresectable, Recurrent Triple Negative Breast Cancer

Running, not enrolling · Phase 2

Conditions studied: Stage III Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer, Invasive Breast Carcinoma, Recurrent Breast Carcinoma, Triple-Negative Breast Carcinoma, Unresectable Breast Carcinoma

In brief

This phase II trial studies how well the combination of avelumab with liposomal doxorubicin with or without binimetinib, or the combination of avelumab with sacituzumab govitecan works in treating patients with triple negative breast cancer that is stage IV or is not able to be removed by surgery (unresectable) and has come back (recurrent). Immunotherapy with checkpoint inhibitors like avelumab require activation of the patient's immune system. This trial includes a two week induction or lead-in of medications that can stimulate the immune system. It is our hope that this induction will improve the response to immunotherapy with avelumab. One treatment, sacituzumab Govitecan, is a monoclonal antibody called sacituzumab linked to a chemotherapy drug called SN-38. Sacituzumab govitecan is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as Tumor-associated calcium signal transducer 2 (TROP2) receptors, and delivers SN-38 to kill them. Another treatment, liposomal doxorubicin, is a form of the anticancer drug doxorubicin that is contained in very tiny, fat-like particles. It may have fewer side effects and work better than doxorubicin, and may enhance factors associated with immune response. The third medication is called binimetinib, which may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may help activate the immune system. It is not yet known whether giving avelumab in combination with liposomal doxorubicin with or without binimetinib, or the combination of avelumab with sacituzumab govitecan will work better in treating patients with triple negative breast cancer.

Key facts

Study ID

NCT03971409

Run by

Laura Huppert, MD, BA

People needed

145

Starts

2019-07-08

Expected to finish

2027-01-31

Last updated by the study team

2026-04-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Signed and dated written informed consent
• Subjects >= 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Clinical stage IV invasive breast cancer or unresectable locoregional recurrence of invasive breast cancer meeting the following criteria:
• Estrogen receptor (ER)/progesterone receptor (PR)-negative (=< 5% cells) by immunohistochemistry (IHC) and human epidermal grow (HER2) negative (by IHC or fluorescence in situ hybridization (FISH))
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria and which can be followed by computed tomography (CT) or magnetic resonance imaging (MRI). A measurable lytic bone lesion(s) and/or skin lesion(s) are allowed. Skin lesions must also be followed by photography with measuring tools within the photograph at each tumor evaluation time point. Ultrasound may be used to follow breast lesions not visible by CT following discussion with Study Chair
• Amenable to biopsy at the time of study entry
• Known tumor/immune cell PD-L1 status by any assay
• Adequate organ function including:
• Cardiac ejection fraction at or above the institutional lower limit of normal, as assessed by either echocardiogram or multigated acquisition (MUGA) scan
• Absolute neutrophil count (ANC) >= 1.0 x 10\^9/L (may have received growth factor)
• Platelets >= 100 x 10\^9/L
• Hemoglobin >= 9 g/dL (may have been transfused)
• Total serum bilirubin =< 1.5 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT/serum glutamate pyruvate transaminase (SGPT)) =< 2.5 x ULN (or =< 5 x ULN if liver metastases are present)
• Serum creatinine =< 1.5 x ULN or estimated creatinine clearance >= 50 mL/min as calculated using the Cockcroft-Gault (CG) equation
• Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x ULN
• Amylase =< 1 x ULN testing is only required in patients with a history of pancreatic disorders (Abnormality not of pancreatic origin is allowed)
• Participants with treated and controlled hypo or hyperthyroidism are eligible.
• Male and female patients of childbearing potential must agree to use at least two methods of acceptable contraception from 15 days prior to first trial treatment administration until at least 30 days after study participant's final dose of study drug(s)
• NOTE: Females of childbearing potential are defined as those who are not surgically sterile or post-menopausal (i.e., patient has not had a bilateral tubal ligation, a bilateral oophorectomy, or a complete hysterectomy; or has not been amenorrhoeic for 12 months without an alternative medical cause). Post-menopausal status in females under 55 years of age should be confirmed with a serum follicle-stimulating hormone (FSH) level within laboratory reference range for postmenopausal women
• Patients unable to read/write in English are eligible to participate in the overall study but will not participate in the Patient-Reported Outcome questionnaires throughout the trial.
• Re-enrollment of a subject that has discontinued the study as a pre-randomization screen failure (i.e., a consented patient who was not randomized and did not receive any study treatment) is permitted. If re-enrolled, the subject must be re-consented. Only the screening procedures performed outside of protocol-specified timing must be repeated; if biopsies and correlative blood samples were already obtained, and patient has not received any systemic anti-cancer therapy since they were obtained, they do not need to be repeated.

You may not qualify if…

• More than 2 lines of chemotherapy in the metastatic setting
• More than 1 prior line of checkpoint inhibitor therapy in the metastatic setting
• Prior treatment with sacituzumab, govitecan
• Concurrent anticancer therapy. Required washout from prior therapies are as follows:
• Chemotherapy: >= 14 days: antibody drug conjugants administered every 3 weeks require a 3-week washout.
• Major surgery: >=14 days (provided wound healing is adequate)
• Radiation: >= 7 days
• Investigational/biologic therapy (half-life =< 40 hours): >= 14 days
• Investigational/biologic therapy (half-life > 40 hours): >= 28 days
• Use of corticosteroids or immunosuppressive medication is exclusionary, except the following in the absence of active autoimmune disease:
• Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intra-articular, intranasal, and inhaled)
• Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent are permitted
• Adrenal replacement steroid doses including doses > 10 mg daily prednisone are permitted
• A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. CT scan premedication against contrast dye allergy) or for treatment of nonautoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by a contact allergen) is permitted
• Previous malignant disease other than breast cancer within the last 5 years, with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or low-risk cancers considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of study drugs AND additional therapy not required while receiving study treatment)
• All subjects with central nervous system metastases and/or carcinomatous meningitis, except those meeting the following criteria::
• Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment
• No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
• Subjects must be either off steroids or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)
• Receipt of any organ transplantation including allogeneic stem-cell transplantation
• Significant acute or chronic infections including, among others:
• Known history of testing positive for human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS); testing is not required for this protocol.
• A history of a positive test for hepatitis B virus (HBV) surface antigen (and/or core antibody) and/or confirmatory hepatitis C virus (HCV) ribonucleic acid (RNA) (if anti-HCV antibody tested positive); testing is not required for this protocol
• Active autoimmune disease with reasonable possibility of clinically significant deterioration when receiving an immunostimulatory agent, per investigator discretion:
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses =< 10 mg or 10 mg equivalent prednisone per day

Where it is running

• O'Neal Comprehensive Cancer Center — Birmingham, Alabama, United States
• University of California, San Francisco — San Francisco, California, United States
• Georgetown University — Washington D.C., District of Columbia, United States
• University of Chicago Medicine Comprehensive Cancer Center — Evergreen Park, Illinois, United States
• Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University — Baltimore, Maryland, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Mayo Clinic — Rochester, Minnesota, United States
• UNC Lineberger Comprehensive Cancer Center — Chapel Hill, North Carolina, United States
• Duke Cancer Institute — Durham, North Carolina, United States
• Abramson Cancer Center, University of Pennsylvania — Philadelphia, Pennsylvania, United States
• Vanderbilt University Ingram Cancer Center — Nashville, Tennessee, United States
• Baylor College of Medicine — Houston, Texas, United States

Full record on ClinicalTrials.gov

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