Innovative Combination Immunotherapy for Metastatic Triple Negative Breast Cancer (TNBC): A Multicenter, Multi-Arm Translational Breast Cancer Research Consortium Study

Who is this study for? Adult patients with advanced triple negative breast cancer
What treatments are being studied? Avelumab
Status: Recruiting
Location: See all (12) locations...
Intervention Type: Drug, Biological
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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.

Locations
United States
Alabama
O'Neal Comprehensive Cancer Center
RECRUITING
Birmingham
California
University of California, San Francisco
RECRUITING
San Francisco
Washington, D.c.
Georgetown University
RECRUITING
Washington D.c.
Illinois
University of Chicago Medicine Comprehensive Cancer Center
RECRUITING
Evergreen Park
Massachusetts
Dana-Farber Cancer Institute
RECRUITING
Boston
Maryland
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
RECRUITING
Baltimore
Minnesota
Mayo Clinic
RECRUITING
Rochester
North Carolina
UNC Lineberger Comprehensive Cancer Center
RECRUITING
Chapel Hill
Duke Cancer Institute
RECRUITING
Durham
Pennsylvania
Abramson Cancer Center, University of Pennsylvania
NOT_YET_RECRUITING
Philadelphia
Tennessee
Vanderbilt University Ingram Cancer Center
RECRUITING
Nashville
Texas
Baylor College of Medicine
ACTIVE_NOT_RECRUITING
Houston
Contact Information
Primary
Amy Langdon
Amy.Deluca@ucsf.edu
415-353-7288
Time Frame
Start Date: 2019-07-08
Estimated Completion Date: 2026-06-30
Participants
Target number of participants: 150
Treatments
Experimental: CLOSED TO ENROLLMENT: Arm I (binimetinib, avelumab)
Patients will receive a 15-day lead-in of binimetinib, followed by binimetinib PO BID and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: CLOSED TO ENROLLMENT: Arm II (anti-OX40 antibody PF-04518600, avelumab)
Patients will receive a 15-day lead-in of anti-OX40 antibody PF-04518600, followed by anti-OX40 antibody PF-04518600 IV over 60 minutes and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: CLOSED TO ENROLLMENT: Arm III (utomilumab, avelumab)
Patients will receive a 15-day lead-in of utomilumab, followed by utomilumab IV over 60 minutes every 4 weeks and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: Arm A (avelumab, binimetinib, liposomal doxorubicin)
Patients receive a 15 day lead-in of binimetinib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity. Patients then receive binimetinib PO BID on days 1-28, avelumab intravenously (IV) over 60 minutes on days 1 and 15, and liposomal doxorubicin IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: Arm B (avelumab, sacituzumab govitecan)
Patients will receive a 15-day lead-in of sacituzumab govitecan given on day -15, followed by sacituzumab govitecan day 8 and day 15 of Cycle (C) 1; day 1,8, and 21 of C2; day 1, 15 and 21 of C3; day 8 and 15 of C4, and schedule continues with two weeks on, one week off for 21-day cycles. Patients also receive 10mg/kg avelumab over 60 minutes on day 1 and day 15 of each 28 day cycle. Cycles repeat in the absence of disease progression or unacceptable toxicity.
Experimental: Arm C (avelumab, liposomal doxorubicin)
Patients will receive a 15-day lead-in of liposomal doxorubicin, followed by liposomal doxorubicin on Day 1 and 10mg/kg avelumab over 60 minutes on Day 1 and Day 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Sponsors
Collaborators: Array BioPharma, Breast Cancer Research Foundation, Pfizer, Translational Breast Cancer Research Consortium, Hoosier Cancer Research Network, Johns Hopkins University, Gilead Sciences
Leads: Laura Huppert, MD, BA

This content was sourced from clinicaltrials.gov