Nivolumab and Eribulin in HER2 Negative Metastatic Breast Cancer (KORNELIA)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seongnam, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Seoul National University Bundang Hospital; Korean Cancer Study Group (KCSG); Eisai Korea Inc.; Ono pharmaceutical Korea
• Investigators: Principal Investigator: JEEHYUN KIM, MD,PhD, Seoul National University Bundang Hospital

Publications and helpful links

Helpful Links

• Korea Cancer Study Group
• Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: August 13, 2019
• First Submitted That Met QC Criteria: August 18, 2019
• First Posted (Actual): August 20, 2019

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 5, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: breast cancer; immunotherapy; PD-1; nivolumab; eribulin; immune checkpoint inhibitor; metastatic breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: KCSG BR18-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No