4545 - Bintrafusp alfa (M7824) and Eribulin Mesylate in Treating Patients With Metastatic Triple Negative Breast Cancer (TNBC)(NCT03579472)

Background

TNBC is an aggressive subtype of metastatic breast cancer. Eribulin has been shown to have activity in metastatic TNBC and has enhanced efficacy if TGF-β is downregulated. Additionally, down-regulating TGF-β in the tumor microenvironment may decrease tumor growth and increase responsiveness to checkpoint blockade. Bintrafusp alfa* (M7824) is an innovative first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. Therefore the combination of eribulin with bintrafusp alfa is being tested in this phase I trial to evaluate safety and efficacy for patients with metastatic TNBC.

Trial design

This is an open-label, single arm phase Ib study in patients with metastatic TNBC. The primary objective is to evaluate the recommended phase-2 dosing of eribulin and bintrafusp. Patients undergo core tissue biopsy and blood work at enrollment. Patients will then receive study drug (bintrafusp alfa) and eribulin with tumor assessments at 6 and 12 weeks. Patients will be treated in a cohort size of 4 with an expansion of up to 20 patients. Bayesian optimal interval (BOIN) design will be employed to identify the RP2D of eribulin by conducting dose de-escalations based on dose-limiting toxicity. Patients undergo repeat core tissue biopsy after 12 weeks of therapy and will continue on study drug until progression of disease or a sustained CR for one year. Eligibility: Inclusion: metastatic TNBC, adequate organ, bone marrow and cardiac parameters. Exclusion: prior immunotherapy, IBC, history of autoimmune disease, HIV, Hep-B, Hep-C, active tuberculosis, pregnant. PD-L1 positivity is not an eligibility requirement. CORRELATIVE SCIENCE: Biopsies and blood are being obtained at baseline and after 2 months of therapy as well as requested at the time of progression of disease. Peripheral blood mononuclear cells (PBMCs will be evaluated for immunophenotyping, T cell activation and function as well as T cell repertoire analysis. PD-L1 staining will be done on tumor and infiltrating immune cells. From the tumor samples, TIL will be measured and characterized as well as tumor-tissue gene expression.

Clinical trial identification

NCT03579472.

Editorial acknowledgement

Legal entity responsible for the study

The University of Texas MD Anderson Cancer Center.

Funding

Merck/EMD-Serono.

Disclosure

J.K. Litton: Research grant / Funding (institution): astra zeneca; Advisory / Consultancy, uncompensated: astra zeneca; Advisory / Consultancy, uncompensated: Pfizer; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Novartis; Advisory / Consultancy, uncompensated: Genentech; Research grant / Funding (institution): Genentech. S. Damodaran: Research grant / Funding (institution): emd serono. I.I. Wistuba: Research grant / Funding (institution): emd serono. L. Ojalvo: Full / Part-time employment: emd serono. I. Dussault: Full / Part-time employment: emd serono. C. Helwig: Full / Part-time employment: Merck. All other authors have declared no conflicts of interest.