A phase 3 open-label, randomized, multicenter study of imprime PGG in combination with cetuximab in patients with KRAS wild type metastatic colorectal cancer

Background: Imprime PGG (Imprime) is a beta‐1,3/1,6 glucan complex carbohydrate biologic, which harnesses innate immune effector cells to enhance killing of antibody‐ targeted, complement‐opsonized tumor cells. In a phase 2 single‐arm clinical trial in metastatic colorectal cancer (mCRC), the combination of Imprime with cetuximab resulted in 24% objective response rate (ORR), 62% disease control rate (DCR), and median time to progression (TTP) of 12 wks (Tamayo ME, Ann Onc 2010), representing approximate 100% increases vs historical control (Cunningham, NEJM 2004). ORR was 45%, DCR, 82% and TTP of 24 wks in patients (pts) with KRAS wild‐type (WT) tumors (post hoc analysis). Single‐agent cetuximab has been shown to improve ORR, progression‐free survival (PFS) and overall survival (OS) in pts with epidermal growth factor receptor (EGFR) expressing, KRAS WT mCRC who failed oxaliplatin‐ and irinotecan‐based therapy or are intolerant to irinotecan. The mechanism of action of cetuximab is thought to rely on competitive blockade of endogenous ligand binding and downstream signaling, internalization and down regulation of EGFR, as well as antibody‐dependent cellular cytotoxicity (ADCC) (Erbitux USPI). The current trial, sponsored by Biothera and registered with ClinicalTrials.gov (NCT01309126 ) is to confirm these findings in phase 3. Methods: Eligible pts have received prior oxaliplatin‐ and irinotecan‐based therapy or are intolerant to irinotecan, have measurable disease and ECOG performance status of 0 or 1. Approximately 795 pts will be randomized 2:1, stratified by geographic region, prior chemotherapy and site, to receive weekly open‐label Imprime plus cetuximab or cetuximab alone. The primary endpoint of the study is OS and the primary analysis will occur when 709 deaths have occurred. Secondary endpoints include PFS, ORR (based on RECIST 1.1), quality of life, safety and pharmacokinetics. Exploratory endpoints include biomarker analyses. Pt screening and enrollment is underway in the United States and Europe.