Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer

AIRE - Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer - a Prospectively Randomized Phase IV Study

After progression of disease after one chemotherapy, metastatic breast cancer patients will be randomized 1:1 to one of the following treatment arms:

Arm A. Eribulin Arm B. Paclitaxel

Blood draws for immune analysis will be performed before start of therapy, on day 1 of cycle 2 and on day 21 of cycle 4 (end of therapy) for the primary study aim. Patients will be treated under study conditions for a maximum of 4 therapy cycles.

This is a prospective, randomized Phase IV study. Patients who progressed after one chemotherapy in the metastatic setting will be randomized 1:1 to one of the following treatment arms. Arm A. Eribulin 1.23 mg/m2 on days 1 and 8 q21d Arm B. Paclitaxel 80 mg/m2 on days 1, 8, and 15 q21d Blood draws for immune analysis will be performed before start of therapy on day 1 of cycle 1, on day 1 of cycle 2 (pre dose each) and on day 21 of cycle 4 (end of therapy) and assessed for the primary study aim. Patients will be treated under study conditions for a maximum of 4 therapy cycles.

Inclusion Criteria:

• Written informed consent prior to beginning of trial specific procedures
• Subject must be female and aged ≥ 18 years on day of signing informed consent
• ECOG 0-1
• Histologically confirmed, HER2 negative breast cancer determined by core biopsy of tumor lesion. Human epidermal growth factor receptor 2 (HER2) negativity is defined as either of the following by local laboratory assessment: In situ hybridization (ISH) non-amplified (ratio ≤ 2.2), or IHC 0 or IHC 1+.
• Indication for chemotherapy
• Previous therapy with one chemotherapy line
• Target lesion (RECIST 1.1)
• Adequate organ function defined as:

Creatinine Clearance > 50 ml/min ANC ≥ 1.5 x 10 3 /μL Thrombocytes > 100 x 10 3 /μL

Exclusion Criteria:

• HER2 positive disease
• Indication for an anti-hormone treatment
• Active infection requiring systemic therapy.
• Active autoimmune disease or other diseases that requires systemic treatment with corticosteroids or immunosuppressive drugs.
• History of primary or acquired immunodeficiency (including allogenic organ transplant).
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• Severely impaired liver function (Child Pugh C)
• Hypersensitivity to study medication or any of its components
• Neuropathy (PNP) > Grade 2 (CTCAE 5.0)
• Congenital long QT syndrome
• Preexisting concomitant use of strong CYP3A4 and CYP2C8 inhibiting or inducing drugs
• Life expectancy of less than three months
• Pregnancy (contraception is required according tocontraceptive guidance)
• Lactation
• Known history of following infections: Human immunodeficiency virus (HIV), History of acute or chronic Hepatitis B or Hepatitis C
• Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
• Does not agree to blood collection