GOBLET Study Tests Pelareorep Plus Atezolizumab in Various GI Cancers

Enrollment in the phase 1/2 GOBLET study of pelareorep (Reolysin) in combination with atezolizumab (Tecentriq) as treatment for patients with metastatic pancreatic, metastatic colorectal, and advanced anal cancers is ongoing, according to an update presented by during the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.¹

The presentation follows news from November 2021, that the firt patient in the study was dosed with pelareorep.²

"There is a pressing unmet need for agents that can synergize with immune checkpoint inhibitors [ICI] in gastrointestinal [GI] cancers, as fewer than half of these patients respond to ICI monotherapy," said Dirk Arnold MD, PhD, director of Asklepios Tumorzentrum Hamburg, and primary investigator of the GOBLET trial. "These low response rates are driven by immunosuppressive tumor microenvironments, which pelareorep has been shown to reverse in prior clinical studies in GI, breast, and hematological cancers. We thus believe pelareorep can increase the proportion of GI cancer patients responding to checkpoint inhibitors and are seeking to validate this hypothesis in the GOBLET study. We are very pleased with the trial's progress to date and look forward to its continued advancement."

GOBLET is an open-label, non-randomized, multiple-cohort, phase 1/2 study. GOBLET enrolled 55 patients. The primary end points are objective response rate (ORR) and safety. The secondary end points are progression-free survival and overall survival. GOBLET will test the pelareorep and atezolizumab combination in 4 cohorts.If a cohort shows promising ORR, it will be expanded into an extension phase 2 which will enroll more patients.3

The first cohort (n = 12) features the patients with first-line advanced/metastatic pancreatic cancer. Patients in this cohort are treated with pelareorep plus atezolizumab plus gemcitabine (Gemzar)/nabpaclitaxel (Abraxane). Cohort 2 (n = 19) will have patients with first-line MSI (microsatellite instability)-high metastatic colorectal cancer. These patients are treated with pelareorep plus atezolizumab.

Cohort 3 (n = 14) will consist of patients with metastatic colorectal cancer who did not tolerate 2 prior lines of treatment. These patients are treated with pelareorep plus atezolizumab plus trifluridine/tipiracil.

The final cohort, cohort 4 (n = 10), is treated with pelareorep plus atezolizumab in second-line unresectable anal cancer. The first 3 patients enrolled into cohort 1 and cohort 3 will be included in the phase 1b of the study where the 3-drug combination will be assessed for safety within the first 28-day cycle prior to enrolling additional patients.

Eligible patients must be 18 years or older, have an ECOG performance score of 0 or 1, evaluable lesions per RECIST v.1.1, and have adequate organ function by the time of enrollment. Patients are excluded if they have had systemic chemotherapy, radiotherapy, or surgery less than 4 weeks before the study; if they have previous immune checkpoint inhibitor treatment, if they have autoimmune disease requiring systemic treatment in the past 2 years, if they currently have pneumonitis or have a history of pneumonitis requiring steroids, or if they have symptomatic brain metastases.

_References

_{1. Oncolytics Biotech® provides enrollment update on multi-indication phase 1/2 gastrointestinal cancer trial at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. News Release. Oncolytics Biotech. January 20, 2022. Accessed January 26, 2022.https://bit.ly/3G4Ktai}

_{2. Oncolytics Biotech® doses first patient in phase 1/2 GOBLET study evaluating pelareorep-anti-pd-l1 combination therapies in gastrointestinal cancers. New release. Oncolytics Biotech. November 3, 2021. Accessed January 26, 2022. https://bit.ly/3KNkXtK}

_{3. Arnold D, Collienne M, Wilkinson G, Loghmani H, Heineman T. 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. Poster presented at 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January 20-22, 2022. San Franciso, CA. Accessed January 25, 2022. https://bit.ly/3fWPMxN}