M7824 and Eribulin Mesylate in Treating Patients With Metastatic Triple Negative Breast Cancer

NCT03579472 | Terminated Phase 1 FDA Drug

• 3 other identifiers: 2017-0500NCI-2018-01140P30CA016672
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

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.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Recommended phase II dose (RP2D)

  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.

  Up to 90 days post-treatment

• Incidence of adverse events

  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.

  Up to 90 days post-treatment

Study Arms (1)

Treatment (bintrafusp alfa, eribulin mesylate)

EXPERIMENTAL

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.

Drug: Bintrafusp Alfa; Drug: Eribulin Mesylate

Interventions

Bintrafusp Alfa DRUG

Given IV

Also known as: Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359C

Treatment (bintrafusp alfa, eribulin mesylate)

Eribulin Mesylate DRUG

Given IV

Also known as: B1939 Mesylate, E7389, ER-086526, Halaven, Halichondrin B Analog

Treatment (bintrafusp alfa, eribulin mesylate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0-1.
• 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.
• Hepatic impairment Child-Pugh \< B7.
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) with the following exception:
• Patients with known Gilbert disease who have serum indirect bilirubin level =\< 3 X ULN may be enrolled. Eribulin dose modification will be needed in patients with hepatic insufficiency according to the US Prescribing Information (product insert)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x ULN with the following exception: patients with liver involvement: AST and/or ALT =\< 5 x ULN.
• Alkaline phosphatase =\< 2.5 x ULN with the following exception: patients with documented liver involvement or bone metastases: alkaline phosphatase =\< 5 x ULN.

You may not qualify if:

• 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 1.
• 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.
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
• Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations.
• Rash must cover less than 10% of body surface area (BSA).
• Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%). No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids).
• Patients with human immunodeficiency virus (HIV)-1 may be eligible if they meet the following conditions:

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Lyndon Baines Johnson General Hospital

Houston, Texas, 77026-1967, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

bintrafusp alfa protein, human; eribulin

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Senthilkumar Damodaran

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: July 6, 2018
• Study Start: May 30, 2018
• Primary Completion: September 21, 2022
• Study Completion: September 21, 2022
• Last Updated: October 31, 2022

Record last verified: 2022-10

Locations

US (2)