Abstract OT1-18-05: A multicenter, open-label, phase 2 study of Imprime PGG and pembrolizumab in patients with metastatic breast cancer who have progressed through prior hormonal therapy
Authors: Stopeck Alison , Gargano Michele , Bose Nandita , Niles Nick , Chisamore Michael , Iglesias Jose 
Published: March 2022

Abstract
Immune checkpoint inhibitors (ICI) have shown limited response in breast cancers, especially the hormone receptor (HR) positive/human epidermal growth factor receptor 2-negative (Her2-) subtype that is considered to be ‘immunologically cold’ in comparison to the TNBC and Her2+ subtypes. Results from Keynote-028 study showed a ORR of 12% to anti-PD1 antibody, pembrolizumab (KEYTRUDA®; PEM) in previously treated HR+/HER2-/programmed death ligand 1-positive (PD-L1-positive) advanced breast cancer patients. With limited options available for these patients, there is a significant unmet need to expand the clinical benefit from ICI to increased numbers of patients. Imprime PGG (Imprime) is a novel beta glucan acting as a pathogen-associated molecular pattern (PAMP) that drives a cascade of immune activating events. Imprime treatment repolarizes the immunosuppressive microenvironment, activates the maturation of antigen presenting cells, and has significantly enhanced the efficacy of ICI therapy in several preclinical tumor models. Imprime has been studied in combination with PEM, in metastatic TNBC and advanced melanoma in a recently completed Ph2 trial (IMPRIME 1) where in TNBC pts the objective response rate (ORR) = 15.9%, disease control rate (DCR) = 54.5%, median duration of response (mDoR)=12.7mo, median progression free survival (mPFS) =2.86 mo, 12-month overall survival (OS) rate = 57.6%, and median OS= 16.4 months. Clinical benefit in IMPRIME 1 was particularly evident in a subset of pts, mTNBC “converters” (12/44 total TNBC pts) who had originally been diagnosed with ER/PR+ disease and progressed through endocrine therapies +/- CDK4/6 inhibitors. In these 12 TNBC converters, the ORR = 50%, DCR = 83%, mDoR=11.2, mPFS=5.6 mo, 12-month OS rate=64.8%, and mOS= 17.4 months. Imprime is now being explored in pts with hormone-resistant metastatic breast cancer (MBC) in combination with PEM. This is a phase 2, Simon’s 2-Stage study of pts with MBC who have progressed through prior hormonal therapy with at least one CDK4/6 inhibitor. All pts will receive Imprime 4 mg/kg/wk + PEM 200 mg Q3wk. A total of 23 pts will be enrolled into Stage 1. If ≥4 pts in Stage 1 have an objective response after 12 wks of treatment, the study will proceed into Stage 2. Twenty-four (24) pts will be enrolled in Stage 2 for a total combined population of 47 pts. Rejection of the null hypothesis will require documenting at least 10 objective responses in the total population. Main eligibility criteria include a diagnosis of MBC having failed prior hormonal therapy with at least one CDK4/6 inhibitor, ≤1 prior line of chemotherapy, serum ABA level of ≥20 µg/mL, and no prior ICI exposure. The primary endpoint is ORR (per RECIST v1.1); secondary endpoints are mPFS, PFS, mOS, OS, DCR, DoR, and safety. Exploratory objectives will assess the impact of the treatment combination on immune activating events in peripheral blood and at the tumor level, and correlate changes in PD-L1 status, the tumor microenvironment, and serum ABA with response. Point estimates with the exact 95% confidence intervals of ORR and DCR will be computed. For mPFS, PFS, mOS, OS, and DoR, medians, first, and third quartiles with 95% confidence intervals (CIs) will be estimated using Kaplan-Meier method. Safety parameters will be summarized. The trial is sponsored by HiberCell, Inc. in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Approximately 25 US sites will participate in the study. For information, contact Nick Niles nniles@hibercell.com. 612.230.5846.
Citation Format: Alison Stopeck, Michele Gargano, Nandita Bose, Nick Niles, Michael Chisamore, Jose Iglesias. A multicenter, open-label, phase 2 study of Imprime PGG and pembrolizumab in patients with metastatic breast cancer who have progressed through prior hormonal therapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-18-05.