Oncolytics Biotech Inc. has announced the Data Safety Monitoring Board (DSMB) recommendation to continue enrollment in Cohort 5 of the GOBLET study, a phase 1/2 trial evaluating pelareorep in combination with modified FOLFIRINOX (mFOLFIRINOX), with or without atezolizumab, for patients with newly diagnosed pancreatic ductal adenocarcinoma (PDAC). This decision follows a review of initial safety data from the trial.
The GOBLET study is a randomized, open-label, multicenter trial assessing the efficacy and safety of pelareorep, an oncolytic reovirus, across multiple gastrointestinal cancers. Cohort 5 specifically focuses on patients with newly diagnosed metastatic PDAC, a population with limited treatment options and poor prognosis.
Study Design and Objectives
The GOBLET study, managed by AIO-Studien-gGmbH, is being conducted at 17 centers in Germany. It includes five cohorts, each targeting different gastrointestinal cancers and treatment combinations. Cohort 5 employs a 3-patient safety run-in phase to evaluate the tolerability of pelareorep with mFOLFIRINOX and atezolizumab, and pelareorep plus mFOLFIRINOX. Following the safety run-in, 15 evaluable patients will be randomly assigned to each arm in stage 1.
The co-primary endpoints of the study are objective response rate (ORR) assessed at week 16 and safety. Secondary endpoints include additional efficacy assessments and evaluation of potential biomarkers, such as T-cell clonality and CEACAM6. If pre-specified criteria are met, either or both arms may advance to stage 2, enrolling an additional 17 patients per arm.
Rationale for Pelareorep in PDAC
According to Thomas Heineman, MD, PhD, Chief Medical Officer at Oncolytics, pelareorep has the potential to improve treatment options for PDAC patients. The current standard of care primarily involves chemotherapy regimens like gemcitabine plus nab-paclitaxel or mFOLFIRINOX. Pelareorep has previously demonstrated synergy with gemcitabine, nab-paclitaxel, and atezolizumab in GOBLET cohort 1, suggesting its potential to enhance the efficacy of mFOLFIRINOX in PDAC.
Heineman also noted that this study builds on cohort 1 by evaluating pelareorep's ability to work with checkpoint inhibitors, which could be a significant advancement, especially since immune therapies have shown limited benefit in most patients with this 'cold' tumor.
Anticipated Updates
Full updates from the trial are expected in 2025, with safety data anticipated to be released in the first half of the year and initial efficacy results planned to follow in the second half. These results could provide valuable insights into the potential of pelareorep-based combination therapies for PDAC.
