A Phase Ib Trial of M7824 and Eribulin in Patients With Metastatic Triple Negative Breast Cancer (TNBC)
Overview
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 38
- Locations
- 2
- Primary Endpoint
- Incidence of adverse events
Overview
Brief Summary
This phase Ib trial studies the best dose and side effects of eribulin mesylate when given together with M7824)in treating patients with triple negative breast cancer that has spread to other places in the body. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as M7824, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving eribulin mesylate and M7824 may work better at treating triple negative breast cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose (RP2D) of eribulin mesylate (eribulin) when in combination with the fixed dose of bintrafusp alfa (M7824) in patients with metastatic triple-negative breast cancer (TNBC).
II. To evaluate the safety and tolerability of M7824 when in combination with eribulin in patients with metastatic TNBC.
SECONDARY OBJECTIVES:
I. To determine the best overall response (BOR) rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
II. To determine the overall response rate (ORR).
OTHER OBJECTIVES:
I. To assess immunologic/molecular responses to M7824 in combination with eribulin in patients with metastatic TNBC.
II. Estimation of progression-free survival (PFS) in metastatic TNBC patients treated with M7824 in combination with eribulin.
III. Perform correlative studies on blood and tissue samples to evaluate systemic and tumor biomarkers of response and resistance to M7824 and eribulin.
IV. Correlative studies on blood and tissue samples will also be used to evaluate systemic and tumor biomarkers of response to M7824 and eribulin.
OUTLINE:
Patients receive bintrafusp alfa intravenously (IV) over 50-80 minutes on days 1, 15, and 29, and eribulin mesylate IV over 2-5 minutes on days 1, 8, 22, and 29. Treatment repeats every 42 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 90 days.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed written informed consent.
- •Histologically confirmed metastatic triple negative breast cancer with measurable disease by RECIST 1.1 criteria
- •Hormone receptor (HR) defined as positive for the purposes of this study, if expression of estrogen receptor (ER) and/or progesterone receptor (PR) expression is greater than 10% by immunohistochemistry (IHC) and HER2 negative or non-amplified is determined by the current American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) criteria, which are as follows: HER2 testing by IHC as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be performed.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Baseline multi-gated acquisition scan (MUGA) or echocardiogram scans with left ventricular ejection fraction (LVEF) of \> 50%.
- •Absolute neutrophil count (ANC) \>= 1500 cells/uL.
- •White blood cell (WBC) counts \> 2500/uL.
- •Lymphocyte count \>= 300/uL.
- •Platelet count \>= 100,000/uL.
- •Hemoglobin \>= 9.0 g/dL.
Exclusion Criteria
- •Women who are pregnant or breast-feeding.
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) for metastatic breast cancer-or- if patient has had prior immune-oncology therapies in the neoadjuvant or adjuvant setting within the past 12 months.
- •Has had major surgery within 21 days before cycle 1, day
- •Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
- •Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association \> class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
- •Serious intercurrent infections or non-malignant medical illness that are uncontrolled or the control of which may be jeopardized by this therapy.
- •Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols.
- •History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.
- •Patients with a history of autoimmune hypothyroidism (such as atrophic thyroiditis) on a stable dose of thyroid replacement hormone may be eligible.
- •Patients with uncontrolled type 1 diabetes mellitus. If on a stable insulin regimen may be eligible, after discussion with principal investigator.
Arms & Interventions
Treatment (bintrafusp alfa, eribulin mesylate)
Patients receive bintrafusp alfa IV over 50-80 minutes on days 1, 15, and 29, and eribulin mesylate IV over 2-5 minutes on days 1, 8, 22, and 29. Treatment repeats every 42 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Intervention: Bintrafusp Alfa (Drug)
Treatment (bintrafusp alfa, eribulin mesylate)
Patients receive bintrafusp alfa IV over 50-80 minutes on days 1, 15, and 29, and eribulin mesylate IV over 2-5 minutes on days 1, 8, 22, and 29. Treatment repeats every 42 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Intervention: Eribulin Mesylate (Drug)
Outcomes
Primary Outcomes
Incidence of adverse events
Time Frame: Up to 90 days post-treatment
Safety and tolerability will be assessed in terms of adverse events (AEs), and serious adverse events (SAEs). AEs and SAEs will be tabulated using frequencies and percentages, by severity, by grade, and by relationship to study treatment.
Recommended phase II dose (RP2D)
Time Frame: Up to 90 days post-treatment
Will be defined as highest dose with dose limiting toxicity (DLT) rate =\< 30%. The number of patients on each dose as well as DLTs will be summarized. Bayesian optimal interval (BOIN) design will be employed to identify the RP2D of eribulin with M7824.
Secondary Outcomes
No secondary outcomes reported