Abstract S1-09: A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer
Authors: Nanda Rita , Chow Laura Q , Dees E  Claire , Berger Raanan , Gupta Shilpa , Geva Ravit , Pusztai Lajos , Dolled-Filhart Marisa , Emancipator Kenneth , Gonzalez Edward J , Houp Jennifer , Pathiraja Kumudu , Karantza Vassiliki , Iannone Robert , Gause Christine K , Cheng Johnathan D , Buisseret Laurence 
Published: May 2015

Abstract
Introduction: The PD-1 receptor-ligand pathway can be used by tumors to evade immune surveillance, thereby allowing neoplastic growth. Pembrolizumab is a highly selective, humanized IgG4/kappa isotype mAb designed to block PD-1 interaction with its ligands PD-L1 and PD-L2, thereby reactivating the immune system to eradicate tumors.
Methods: This is a multi-center, non-randomized trial of single agent MK-3475 treatment given intravenously at 10 mg/kg every 2 weeks, in patients with recurrent/metastatic triple-negative (ER, PR, and HER2 negative) breast cancer (TNBC). PD-L1 expression in tumor or stroma was required for study entry. PD-L1 status was determined by immunohistochemical analysis of patient’s tumor tissues using the Merck proprietary 22C3 antibody. Primary objectives of this study were to determine the safety, tolerability, and anti-tumor activity of MK-3475 in patients with PD-L1 positive, advanced TNBC. Secondary objectives included assessments of progression-free survival, overall survival, and response duration. Adverse events (AEs) reported in any patient receiving at least 1 dose of study treatment were monitored and graded using NCI CTCAE v. 4.0. Radiographic imaging was obtained every 8 weeks and evaluated by both investigator and an independent radiologist to assess clinical responses as defined by RECIST 1.1. This study (Clinicaltrials.gov: NCT01848834) is being conducted in conformance with Good Clinical Practices.
Results: A total of 32 female patients with a median age of 50.5 years (range 29 – 72 years) with PD-L1 positive, recurrent/metastatic TNBC were enrolled in the study. Most of these patients had received and progressed on multiple lines of therapy for advanced disease. A preliminary analysis of data collected as of 23May2014 indicates that 5 patients (15.6%) experienced at least one drug-related serious adverse event (SAE); each of 4 patients experienced one of the following: Grade 3 anemia, headache, aseptic meningitis or pyrexia, and a fifth patient experienced disseminated intravascular coagulation (DIC) with thrombocytopenia and decreased blood fibrinogen. The patient who experienced DIC died. Preliminary analysis of data collected from investigators as of 23May2014 indicates that no patient had a complete response, 16.1% of patients had a partial response, 9.7% had stable disease, and 64.5% had progressive disease. As of 23May2014, all but one of the responders, in addition to three patients with stable disease, remain on treatment.
Conclusion: This is the first report of clinical activity of an immune checkpoint inhibitor in TNBC. The preliminary results from this study suggest that single agent MK-3475 is a well-tolerated and effective treatment with significant therapeutic activity in a subset of heavily pre-treated patients with recurrent/metastatic triple-negative breast cancer.
Citation Format: Rita Nanda, Laura Q Chow, E Claire Dees, Raanan Berger, Shilpa Gupta, Ravit Geva, Lajos Pusztai, Marisa Dolled-Filhart, Kenneth Emancipator, Edward J Gonzalez, Jennifer Houp, Kumudu Pathiraja, Vassiliki Karantza, Robert Iannone, Christine K Gause, Johnathan D Cheng, Laurence Buisseret. A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S1-09.