Abstract OT1-01-04: A phase 2, open-label study of imprime PGG (Imprime), a novel beta glucan, with pembrolizumab (Pembro) in chemotherapy-resistant metastatic triple negative breast cancer (TNBC)
Authors: O'Day SJ , Stopeck AT , Huhn RD , Gargano MA , Prathikanti R , Ma B , Mattson PM , Lowe JR , Bose N , Ertelt KE , Ottoson NC , Uhlik MT , Graff JR , Chisamore MJ 
Published: February 2018

Abstract
By blocking the interaction of PD-L1 with PD-1, immune checkpoint inhibitors (CPI) can unleash specific, anti-cancer killing function of activated cytotoxic T cells in patients (pts) for whom there is evidence of an ongoing anti-cancer immune response (PD-L1 expression and/or activated T cells within the tumor bed). Single agent CPI therapy has provided substantial clinical benefit to pts with multiple cancer types. Though effective, response rates are typically limited (˜15-30% of pts depending on tumor type) and therapy fails to benefit the majority of pts. For these pts there is often limited or no evidence of an ongoing T cell-based immune response. Agents that stimulate the anti-cancer immune response may be particularly promising in expanding the clinical responsiveness to CPI therapies. Imprime is a novel beta glucan derived from Saccharomyces acting mechanistically as a pathogen-associated molecular pattern (PAMP) or non-self danger signal, to awaken and activate the innate immune system. Imprime drives a cascade of immune activating events activating tumor-specific cytotoxic T cells. Imprime treatment elicits repolarization of the immunosuppressive microenvironment while activating the maturation of antigen presenting cells. Imprime has significantly enhanced the efficacy of CPI therapy in preclinical tumor models. In humans, Imprime-mediated innate immune activation requires the formation of an immune complex with naturally-occurring anti-beta glucan antibodies (ABA). Formation of this complex is dependent upon sufficient ABA levels. Imprime is now being studied in combination with pembro (KEYTRUDA®), a humanized mAb against PD-1 which has been previously studied in TNBC pts.This phase 2 study explores the treatment combination in pts with metastatic TNBC who progressed following at least one line of chemotherapy and pts with metastatic melanoma who progressed following CPI therapy with sufficient pre-treatment ABA levels (˜50% of screened patients). The study is a Simon 2-stage design. Specific to the TNBC tumor type, a sample size of 12 pts in Stage 1 is planned. Criteria to advance to Stage 2 are ≤4 GR 3/4 AEs and ≥2 objective responses in TNBC. An additional 30 TNBC pts may be enrolled in Stage 2. Main eligibility criteria are metastatic TNBC after chemotherapy in the metastatic setting and serum ABA ≥20 µg/mL. The primary endpoints are ORR and safety; secondary endpoints are TTR, CRR, DoR, PFS, and OS. Efficacy will be analyzed for ORR and CRR as point estimates with 95% CI and for PFS, OS, DoR and TTR as descriptive summaries. Safety parameters will be summarized. Exploratory endpoints include ORR and PFS based on irRECIST. This study aims to collect pre- and early on-treatment tumor (6 wks post-1st dose) biopsies and peripheral blood to assess the impact of the treatment combination on immune activating events in the periphery and at the tumor site. As of June 2017, 11 sites were open and 4 pts were in treatment. The trial is sponsored by Biothera Pharmaceuticals, Inc. in collaboration with Merck & Co. (ClinicalTrials.gov NCT02981303) For information, contact Richard D. Huhn, MD, Biothera Med Dir at rhuhn@biothera.com or 651-256-4657.
Citation Format: O'Day SJ, Stopeck AT, Huhn RD, Gargano MA, Prathikanti R, Ma B, Mattson PM, Lowe JR, Bose N, Ertelt KE, Ottoson NC, Uhlik MT, Graff JR, Chisamore MJ. A phase 2, open-label study of imprime PGG (Imprime), a novel beta glucan, with pembrolizumab (Pembro) in chemotherapy-resistant metastatic triple negative breast cancer (TNBC) [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 OT1-01-04.