Avelumab With Binimetinib, Sacituzumab Govitecan, or Liposomal Doxorubicin in Treating Stage IV or Unresectable, Recurrent Triple Negative Breast Cancer
InCITe
Innovative Combination Immunotherapy for Metastatic Triple Negative Breast Cancer (TNBC): A Multicenter, Multi-Arm Translational Breast Cancer Research Consortium Study
4 other identifiers
interventional
145
1 country
12
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2019
Longer than P75 for phase_2
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 29, 2019
CompletedFirst Posted
Study publicly available on registry
June 3, 2019
CompletedStudy Start
First participant enrolled
July 8, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2027
April 17, 2026
April 1, 2026
7.6 years
May 29, 2019
April 14, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Best Overall Response Rate (BORR)
BORR is defined as the percentage of patients achieving complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and will be reported for each arm along with 95% two-sided confidence intervals.
From treatment initiation until disease progression, an estimated average of 1 year
Secondary Outcomes (13)
Overall Response Rate (ORR)
From treatment initiation until disease progression, an estimated average of 1 year
Clinical Benefit Rate (CBR)
6 months
Median Progression-free Survival (PFS)
From treatment initiation until disease progression, an estimated average of 1 year
Median Overall Survival (OS)
12 months
Percentage of participants with treatment-related adverse events
Up to 30 days after completion of study treatment, approximately 13 months
- +8 more secondary outcomes
Study Arms (6)
CLOSED TO ENROLLMENT: Arm I (binimetinib, avelumab)
EXPERIMENTALPatients 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.
CLOSED TO ENROLLMENT: Arm II (anti-OX40 antibody PF-04518600, avelumab)
EXPERIMENTALPatients 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.
CLOSED TO ENROLLMENT: Arm III (utomilumab, avelumab)
EXPERIMENTALPatients 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.
Arm A (avelumab, binimetinib, liposomal doxorubicin)
EXPERIMENTALPatients 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.
Arm B (avelumab, sacituzumab govitecan)
EXPERIMENTALPatients 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.
Arm C (avelumab, liposomal doxorubicin)
EXPERIMENTALPatients 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.
Interventions
Given IV
Given IV
Given PO
Given IV
Given IV
Given IV
Eligibility Criteria
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)
- +8 more criteria
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
- 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::
- +24 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Laura Huppert, MD, BAlead
- Translational Breast Cancer Research Consortiumcollaborator
- Hoosier Cancer Research Networkcollaborator
- Array BioPharmacollaborator
- Pfizercollaborator
- Breast Cancer Research Foundationcollaborator
- Johns Hopkins Universitycollaborator
- Gilead Sciencescollaborator
Study Sites (12)
O'Neal Comprehensive Cancer Center
Birmingham, Alabama, 35294, United States
University of California, San Francisco
San Francisco, California, 94143, United States
Georgetown University
Washington D.C., District of Columbia, 20057, United States
University of Chicago Medicine Comprehensive Cancer Center
Evergreen Park, Illinois, 60805, United States
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
Baltimore, Maryland, 21218, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Duke Cancer Institute
Durham, North Carolina, 27710, United States
Abramson Cancer Center, University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Vanderbilt University Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Laura Huppert, MD
University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Assistant Clinical Professor
Study Record Dates
First Submitted
May 29, 2019
First Posted
June 3, 2019
Study Start
July 8, 2019
Primary Completion (Estimated)
January 31, 2027
Study Completion (Estimated)
January 31, 2027
Last Updated
April 17, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share