Nivolumab and Eribulin in HER2 Negative Metastatic Breast Cancer

Study Overview
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Brief Summary
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Cancer therapeutics such as chemotherapy may modulate tumor/immune-system interactions in favor of the immune system. Chemotherapy can result in tumor cell death with a resultant increase in tumor antigen delivery to antigen-presenting cells. Therefore, combining immunotherapy (Nivolumab) with chemotherapy (Eribulin) is a promising anti-cancer strategy.

Official Title
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A Phase IB/II, Single Arm, Multi-center Study of Nivolumab in Combination With Eribulin in HER2 Negative Metastatic Breast Cancer Patients

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures Age 20 years or older ECOG performance status(PS) 0 or 1 Histologically confirmed stage IV or recurrent breast cancer HER2 negative disease: not eligible for anti-HER2 therapy * HER2 negative [IHC 0, 1+ or IHC 2+ with corresponding ISH non-amplified or ratio less than 2.0 or ISH non-amplified ratio less than 2.0] as per ASCO-CAP HER2 guideline recommendations 2013 (ASCO-CAP) Patients previously treated with anthracycline and/or taxane unless contraindicated; Patients who received anthracycline and/or taxane based chemotherapy in either the neoadjuvant, adjuvant or metastatic setting and experienced disease progression on or after taxane-based chemotherapy in the metastatic setting No more than 3 prior lines of cytotoxic chemotherapy for metastatic disease; patients who experienced disease recurrence within 1 year after completion of (neo)adjuvant anthracycline and taxane-based chemotherapy will be counted as 1 prior line of treatment.; hormonal therapy will not be counted as a prior line of treatment Measurable disease according to RECIST v 1.1. Exclusion Criteria: Previous treatment with eribulin mesylate or any anti-PD-1, PD-L1, or PD-L2 Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment. Known central nervous system (CNS) disease, except for those subjects with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period Known history of human immunodeficiency virus (HIV) positive Known active hepatitis B or hepatitis C (eg, HCV RNA detected) Any other malignancy that required treatment or has shown evidence of recurrence (except for nonmelanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ) during the 3 years prior to enrollment in this study History of significant cardiovascular disease Hypersensitivity to the active substance or any other excipients of the eribulin mesylate drug product, or to nivolumab Scheduled for major surgery during the study Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be allowed Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis Has a history of interstitial lung disease Has received a live-virus vaccination within 30 days of planned start of study therapy. Seasonal flu vaccines that do not contain live virus are permitted.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: ER+/HER2- BC cohort: 45 pts ER-/HER2- (Triple negative) BC cohort: 45 pts
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ER+/HER2- breast cancer<br>will be treated with a combination of eribulin and nivolumab | Drug: Nivolumab<br>* Nivolumab 360mg on D1 every 3 weeks Eribulin 1.4mg/m2 on D1, 8 every 3 weeks<br>* Other names: Opdivo;|
| Experimental: ER-/HER2- breast cancer<br>will be treated with a combination of eribulin and nivolumab | Drug: Nivolumab<br>* Nivolumab 360mg on D1 every 3 weeks Eribulin 1.4mg/m2 on D1, 8 every 3 weeks<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 months progression-free survival (PFS) rate |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate by RECIST criteria v 1.1 |  | 2 years | 
| Overall survival (OS) |  | 2 years (upto 5 years) | 
| Incidence Rate of each Toxicity by CTCAE 4.0 |  | 2 years (upto 5 years) | 
| Clinical benefit rate by RECIST criteria v 1.1 (and iRECIST) |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, eribulin, nivolumab, immunotherapy, immune checkpoint inhibitor, metastatic breast cancer, PD-1