Positive Safety Reported on Frontline Pelareorep in Metastatic Colorectal Cancer

No safety concerns were observed with frontline pelareorep (Reolysin) in patients with metastatic colorectal cancer (mCRC), according to a Data Safety Monitoring Board (DSMB) review of the safety run-in analysis in the phase 1/2 GOBLET study.¹

Based on the results from the 3 patients in the safety run-in analysis, the DSMB suggests that the study continue to full enrollment pending clearance by the Paul Ehrlich Institute (PEI), Germany's medical regulatory body.Recently, the PEI cleared the study's pancreatic cancer cohort for full enrollment after the DSMB made a similar recommendation. The trial's anal cancer and first-line mCRC cohorts do not include safety run-ins and are proceeding as planned.

The GOBLET study is an open-label, non-randomized, multiple-cohort, phase 1/2 study designed to evaluate the safety and efficacy of pelareorep (Reolysin) in combination with Roche's anti-PD-L1 checkpoint inhibitor atezolizumab (Tecentriq) in patients with metastatic pancreatic, metastatic colorectal, and advanced anal cancers.²This study is managed by AIO, an academic cooperative medical oncology group, across 14 clinical trial sites in Germany.

The coprimary end points of the study are objective response rate (ORR) assessed at week 16 and safety. The secondary end points are additional efficacy assessments and evaluation of potential biomarkers, such as T-cell clonality and CEACAM6.

"The successful completion of GOBLET's final safety run-in underscores the trial's strong momentum and supports the ability of pelareorep to be safely combined with checkpoint inhibitors," said Thomas Heineman, MD, PhD, chief medical officer of oncolytics. "This achievement positions us to continue building on prior clinical data that demonstrate the potential of pelareorep to provide a clinical benefit in colorectal and other gastrointestinal (GI) cancers. Existing data suggest this clinical benefit likely results from the stimulation of protective immune responses that may be enhanced by the addition of checkpoint inhibition. Given the high prevalence of [gastrointestinal] malignancies, including colorectal and pancreatic cancer, and the fact that most cases do not respond to checkpoint inhibition, we view GOBLET as an important opportunity to evaluate a novel therapeutic approach that may address a pressing unmet medical need."

Prior clinical data, demonstrating adaptive anti-tumor immune responses and a 90% clinical benefit rate in patients with a pelareorep-based combination who have with KRAS-mutated mCRC treated, support the GOBLET study's metastatic colorectal cancer cohorts.³

The GOBLET study expects to enroll 55 patients in a Simon 2-stage design with Stage 1 comprising four treatment groups. The first group would receive pelareorep in combination with atezolizumab, gemcitabine (Gemzar), and nab-paclitaxel (Abraxane) in the first line for patients with metastatic pancreatic cancer; the second group would receive pelareorep in combination with atezolizumab in the first line for patients with microsatellite instability (MSDI)-high mCRC; the third group would receive pelareorep in combination with atezolizumab and TAS-102 in the third line for patients with mCRC; and the final group would receive pelareorep in combination with atezolizumab in the second line for patients with advanced and unresectable anal cancer.

_References

_{1. Oncolytics biotech provides positive safety update on the third-line metastatic colorectal cancer cohort of its multi-indication phase 1/2 gastrointestinal cancer trial. Press release. PR Newswire; March 31, 2022. Accessed March 31, 2022. https://prn.to/38hJbNW}

_{2. Arnold D, Collienne M, Wilkinson GA, Loghmani H, Heineman TC. GOBLET: a phase 1/2 multiple-indication biomarker, safety, and efficacy study in advanced or metastatic gastrointestinal cancers exploring treatment combinations with pelareorep and atezolizumab. J Clin Oncol. Journal of Clinical Oncology. doi: 10.1200/JCO.2022.40.4_suppl.TPS216 Journal of Clinical Oncology 40, no. 4_suppl}

_{3. Goel S, Ocean AJ, Parakrama RY, et al. Elucidation of pelareorep pharmacodynamics in a phase 1 trial in patients with KRAS-mutated colorectal cancer. Mol Cancer Ther. 2020;19(5):1148-1156. doi:10.1158/1535-7163.MCT-19-1117}