atezolizumab + pelareorep

The combination of atezolizumab and pelareorep is being investigated as a treatment for various gastrointestinal cancers, particularly pancreatic, colorectal, and anal cancers. This combination represents a novel approach that pairs an immune checkpoint inhibitor (atezolizumab) with an oncolytic virus (pelareorep). Pelareorep is a naturally occurring, non-genetically modified reovirus that selectively infects and kills tumor cells while promoting immunologic changes that prime tumors to respond to checkpoint blockade therapy. Upon intravenous administration, pelareorep selectively targets cancer cells and stimulates a pro-inflammatory response that enhances tumor susceptibility to immune attack. Atezolizumab (brand name Tecentriq) is a PD-L1 inhibitor that works by blocking the interaction between PD-L1 and its receptors, thereby enabling the activation of T cells and restoring their ability to effectively detect and attack tumor cells. The combination is being evaluated in the GOBLET study, a phase 1/2 platform trial investigating pelareorep-based therapies across multiple gastrointestinal cancer indications. The study includes several cohorts: - Pelareorep with atezolizumab in first-line MSI-high metastatic colorectal cancer - Pelareorep with atezolizumab and TAS-102 in third-line metastatic colorectal cancer - Pelareorep with atezolizumab in second-line advanced and unresectable anal cancer - Pelareorep with modified FOLFIRINOX with or without atezolizumab in newly diagnosed metastatic pancreatic ductal adenocarcinoma (PDAC) In pancreatic cancer, the combination of pelareorep, atezolizumab, gemcitabine, and nab-paclitaxel achieved an impressive 69% objective response rate, including one complete response and eight partial responses. This significantly outperformed the historical control of gemcitabine plus nab-paclitaxel alone (25%). For anal cancer, the combination of pelareorep and atezolizumab demonstrated a 33-37.5% objective response rate in patients with relapsed squamous cell carcinoma of the anal canal, including one patient with a complete response that persisted for over 15 months. This is notable because historical response rates to checkpoint inhibitor monotherapy in this indication are generally only 10-24%. Safety data from the GOBLET study indicates that the combination has a manageable safety profile. Common adverse events include pyrexia (61%), thrombocytopenia (39%), and chills (6%). In the pancreatic cancer cohort with modified FOLFIRINOX, all 9 patients experienced at least one adverse effect, with 7 experiencing grade 3 or higher adverse events, but no treatment-related deaths were reported.