Abstract OT1-02-01: A phase II study of anti-PD-1 (MK-3475) therapy in patients with metastatic inflammatory breast cancer (MIBC) or non-IBC triple negative breast cancer (non-IBC TNBC) who have achieved clinical response or stable disease to prior chemotherapy
Authors: Willey JS , Parker CA , Valero V , Lim B , Reuben JM , Krishnamurthy S , Gong Y , Scoggins ME , Dryden MJ , Liu DD , Woodward WA , Ueno NT 
Published: February 2018

Abstract
Primary Objective: To assess the efficacy of MK-3475 as a single agent in patients with MIBC and non-IBC TNBC. The primary endpoint is disease control rate at the end of 4 months after receiving the treatment. We will also investigate the association between biomarkers in the peripheral blood and tumor tissue, safety and efficacy.
Background: The extensive invasion of lymphatic vessels by tumor emboli in patients with IBC suggests that the host immune surveillance system is suboptimal or that the tumor cells have decreased immunogenicity through immune editing to avoid detection by the host. In the immune-competent host, tumor cells must overcome both innate and adaptive immunologic defenses of the host. The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress immune control. MK-3475 is a potent and highly selective humanized mAb designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. MK-3475 strongly enhances T lymphocyte immune responses in cultured blood cells from healthy human donors, cancer patients, and primates. Mouse anti-PD-1, as a monotherapy, demonstrated efficacy in several syngeneic mouse tumor models. To date, no specific targeted therapeutic options exist for the treatment of MIBC and TNBC. After patients achieving a clinical response to systemic therapy, the maintenance of disease control is not guaranteed. Further, our recent publication suggests that IBC has immune dysfunction. Chemotherapies can debulk the disease volume but cannot be used for maintenance due to their toxicities. Using an anti PD-1 monoclonal antibody is a promising approach for this patient population.
Study Design and Treatment Plan: This is a single arm phase II study. Up to 35 patients with HER2 negative MIBC or metastatic TN-IBC (MTNBC) who have achieved clinical response or stable disease after receiving any prior systemic therapy for metastatic/recurrent disease, and meet all other criteria will be eligible. Patients will receive MK-3475 200 mg IV every 3 weeks for up to 2 years.
Statistical Considerations: The trial will be conducted using Simon's optimal two-stage design and the rate of disease control will be estimated accordingly. It is assumed that the MK-3475 single agent will have a disease control rate of 30%. A disease control rate of 10% or lower will be considered treatment failure and the regimen will be rejected under this circumstance.
Status of the study:
Activation Date: June 2015. 13 patients have been enrolled. Enrollment continues.
Sponsor: Merck Sharp & Dohme Corp.
State of Texas appropriation for rare and aggressive breast cancer research.
Citation Format: Willey JS, Parker CA, Valero V, Lim B, Reuben JM, Krishnamurthy S, Gong Y, Scoggins ME, Dryden MJ, Liu DD, Woodward WA, Ueno NT. A phase II study of anti-PD-1 (MK-3475) therapy in patients with metastatic inflammatory breast cancer (MIBC) or non-IBC triple negative breast cancer (non-IBC TNBC) who have achieved clinical response or stable disease to prior chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-02-01.