A multicenter, open-label, phase II study of PGG beta-glucan and pembrolizumab in patients (pts) with advanced melanoma (MEL) following progression on treatment with checkpoint inhibitors (CPI) or triple negative breast cancer (TNBC) failing front-line chemotherapy for metastatic disease

• Published in: Journal of clinical oncology Vol. 35; no. 15_suppl; p. TPS3105
• Main Authors: Iglesias, Jose Luis, Prathikanti, Radha, Ma, Bo, Mattson, Paulette, Kedrowski, Deb, Lowe, Jamie, Bose, Nandita, Ertelt, Katie E., Ottoson, Nadine, Uhlik, Mark T., Graff, Jeremy, Huhn, Richard Dale, Chisamore, Michael Jon
• Format: Journal Article
• Language: English
• Published: 20.05.2017
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2017.35.15_suppl.TPS3105

Abstract only TPS3105 Background: Imprime PGG (Imprime) is a Pathogen- Associated Molecular Pattern that enhances innate immune cell killing, counteracts immune suppression and triggers activation and maturation of antigen presenting cells. Imprime’s ability to trigger a coordinated innate and adaptive immune response is critical for enhancing the efficacy of CPIs in several pre-clinical tumor models. We are now exploring the combination of PGG beta-glucan and Pembrolizumab, a humanized mAb against programmed death receptor-1 (PD-1) in the clinic. In previous trials, Pembro yielded a 33% ORR and 23 mo mOS in 655 pts with advanced MEL and an 18.5% ORR and 11.2 mo mOS in 27 evaluable pts with metastatic/recurrent TNBC (Ribas et al., 2016; Nanda et al., 2016). Pre-treatment levels of anti-beta glucan antibodies (ABA) are correlated with pt response to Imprime. Methods: This Phase 2 study is enrolling ABA positive pts with advanced MEL following progression on treatment with a CPI or metastatic TNBC failing front-line chemotherapy. The study is a Simon optimal 2-stage design with sample size of 12 pts of each tumor type in Stage 1. If response and AE criteria (≤ 4 [or ≤ 33%] pts with grade 3/4 in Cycle 1) for each tumor type are met, an additional 17 pts with MEL and 30 pts with TNBC will be enrolled in Stage 2. Primary endpoints of the study are ORR (based on RECIST 1.1) and safety. Secondary endpoints include TTR, CRR, DoR, PFS, and OS. PK data will be profiled. Exploratory endpoints include ORR and PFS based on irRECIST, analysis of an ABA biomarker, immune cell activation markers, and changes in the tumor immune microenvironment. Screening and enrollment are underway in the US. Biothera Pharmaceuticals, Inc. is sponsoring the trial (ClinicalTrials.gov NCT02981303) under a collaborative agreement with Merck. Clinical trial information: NCT02981303.