RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2019-07-08

Study Completion:2025-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03971409

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Signed and dated written informed consent 2. Subjects \>= 18 years of age 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 4. 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 5. 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. 6. 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) 7. 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. 8. 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.	1. More than 2 lines of chemotherapy in the metastatic setting 2. More than 1 prior line of checkpoint inhibitor therapy in the metastatic setting 3. Prior treatment with sacituzumab, govitecan 4. 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 5. 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) 6. 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) 7. Receipt of any organ transplantation including allogeneic stem-cell transplantation 8. 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 9. 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 * Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable 10. History of interstitial lung disease that is symptomatic or which may interfere with the detection or management of suspected drug-related pulmonary toxicity 11. Uncontrolled asthma (defined as having 3 or more of the following features of partially controlled asthma within 28 days prior to starting study treatment: Daytime symptoms more than twice per week, any limitation of activities, any nocturnal symptoms/awaking, need for reliever/rescue inhaler more than twice per week, or known lung function \[peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1)\] without administration of a bronchodilator that is \< 80% predicted or personal best \[if known\]) 12. Current symptomatic congestive heart failure (New York Heart Association \> class II), unstable cardiac arrhythmia requiring therapy (e.g. medication or pacemaker), unstable angina (e.g. new, worsening or persistent chest discomfort), uncontrolled hypertension (systolic \> 160 mmHg or diastolic \> 100mmHg), or known cardiac ejection fraction below the lower limit of institutional normal. Or any of the following occurring within 6 months (180 days) prior to first dose of avelumab: Myocardial infarction, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack. (Use of antihypertensive medication to control blood pressure is allowed.) 13. Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK) 14. History of acute or chronic pancreatitis 15. History or current evidence of retinal vein occlusion (RVO), or current risk factors for RVO including uncontrolled glaucoma, ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes (patients with a history of pulmonary embolism or deep vein thrombosis (DVT) are allowed on study if they are also on anticoagulation as noted in (16) below) ; history of retinal degenerative disease. 16. Requirement of anticoagulant therapy with oral vitamin K antagonists such as Coumadin (warfarin). Low-dose anticoagulants for the maintenance of patency in a central venous access device or the prevention of deep vein thrombosis or pulmonary embolism is allowed. Therapeutic use of low molecular weight heparin or factor Xa inhibitors are allowed provided patients are safely able to interrupt it prior to biopsy procedures. 17. Persisting toxicity related to prior therapy that has not reduced to grade 1 (National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0); however, alopecia and sensory neuropathy grade =\< 2 is acceptable 18. Known severe (grade \>= 3 NCI-CTCAE v5.0) hypersensitivity reactions to monoclonal antibodies, or history of anaphylaxis 19. Vaccination within 28 days of the first dose of study drugs and while on trial is prohibited, except for administration of inactivated vaccines (for example, inactivated influenza vaccine) 20. Pregnant or breastfeeding females 21. Known current alcohol or drug abuse 22. Prisoners or subjects who are involuntarily incarcerated 23. Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the patient's study physician to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with scheduled visits, treatment schedule, laboratory tests and other study requirements.

Inclusion Criteria

Exclusion Criteria

1. Signed and dated written informed consent
2. Subjects \>= 18 years of age
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
4. 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
5. 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.
6. 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)
7. 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.
8. 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.

1. More than 2 lines of chemotherapy in the metastatic setting
2. More than 1 prior line of checkpoint inhibitor therapy in the metastatic setting
3. Prior treatment with sacituzumab, govitecan
4. 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
5. 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)
6. 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)
7. Receipt of any organ transplantation including allogeneic stem-cell transplantation
8. 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
9. 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
* Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable
10. History of interstitial lung disease that is symptomatic or which may interfere with the detection or management of suspected drug-related pulmonary toxicity
11. Uncontrolled asthma (defined as having 3 or more of the following features of partially controlled asthma within 28 days prior to starting study treatment: Daytime symptoms more than twice per week, any limitation of activities, any nocturnal symptoms/awaking, need for reliever/rescue inhaler more than twice per week, or known lung function \[peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1)\] without administration of a bronchodilator that is \< 80% predicted or personal best \[if known\])
12. Current symptomatic congestive heart failure (New York Heart Association \> class II), unstable cardiac arrhythmia requiring therapy (e.g. medication or pacemaker), unstable angina (e.g. new, worsening or persistent chest discomfort), uncontrolled hypertension (systolic \> 160 mmHg or diastolic \> 100mmHg), or known cardiac ejection fraction below the lower limit of institutional normal. Or any of the following occurring within 6 months (180 days) prior to first dose of avelumab: Myocardial infarction, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack. (Use of antihypertensive medication to control blood pressure is allowed.)
13. Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK)
14. History of acute or chronic pancreatitis
15. History or current evidence of retinal vein occlusion (RVO), or current risk factors for RVO including uncontrolled glaucoma, ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes (patients with a history of pulmonary embolism or deep vein thrombosis (DVT) are allowed on study if they are also on anticoagulation as noted in (16) below) ; history of retinal degenerative disease.
16. Requirement of anticoagulant therapy with oral vitamin K antagonists such as Coumadin (warfarin). Low-dose anticoagulants for the maintenance of patency in a central venous access device or the prevention of deep vein thrombosis or pulmonary embolism is allowed. Therapeutic use of low molecular weight heparin or factor Xa inhibitors are allowed provided patients are safely able to interrupt it prior to biopsy procedures.
17. Persisting toxicity related to prior therapy that has not reduced to grade 1 (National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0); however, alopecia and sensory neuropathy grade =\< 2 is acceptable
18. Known severe (grade \>= 3 NCI-CTCAE v5.0) hypersensitivity reactions to monoclonal antibodies, or history of anaphylaxis
19. Vaccination within 28 days of the first dose of study drugs and while on trial is prohibited, except for administration of inactivated vaccines (for example, inactivated influenza vaccine)
20. Pregnant or breastfeeding females
21. Known current alcohol or drug abuse
22. Prisoners or subjects who are involuntarily incarcerated
23. Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the patient's study physician to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with scheduled visits, treatment schedule, laboratory tests and other study requirements.

Contacts and Locations

Study Contact

Hope Rugo, MD

CONTACT

877-827-3222

cancertrials@ucsf.edu

Amy Langdon

CONTACT

415-353-7288

Amy.Deluca@ucsf.edu

Principal Investigator

Hope Rugo, MD

PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Study Locations (Sites)

O'Neal Comprehensive Cancer Center

Birmingham, Alabama, 35294

United States

University of California, San Francisco

San Francisco, California, 94143

United States

Georgetown University

Washington, 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

Collaborators and Investigators

Sponsor: Hope Rugo, MD

Hope Rugo, MD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-07-08

Study Completion Date2025-06-30

Study Record Updates

Study Start Date2019-07-08

Study Completion Date2025-06-30

Terms related to this study

Additional Relevant MeSH Terms

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