NEW YORK – Oncolytics Biotech on Wednesday said it has dosed the first patient in a Phase I/II trial exploring the activity of its immunotherapeutic agent pelareorep plus Roche's PD-L1 inhibitor atezolizumab (Tecentriq) in various metastatic gastrointestinal tumors.
The GOBLET trial will enroll 55 patients across four cohorts at cancer centers in Germany. One cohort will include metastatic pancreatic cancer patients and explore first-line treatment with pelareorep, atezolizumab, gemcitabine, and nab-paclitaxel. There will be two colorectal cancer cohorts: One will include microsatellite instability-high metastatic colorectal cancer patients for first-line treatment with pelareorep and atezolizumab, and another will explore third-line treatment with pelareorep, atezolizumab, and TAS-102 (Taiho Oncology's Lonsurf) in metastatic colorectal cancer patients. The fourth cohort will involve patients with advanced and unresectable anal cancer who receive second-line treatment with pelareorep and atezolizumab.
The primary endpoint of the study is safety. The company will also assess overall survival and explore whether CEACAM6 expression and T-cell clonality can predict which patients will benefit from the combo treatment. The biomarker insights may guide the design of future studies.
In a previous study of pelareorep in pancreatic cancer, patients with low levels of CEACAM6 mRNA expression had longer progression-free survival than those with high CEACAM6 expression. Another study of pelareorep plus chemotherapy also showed activity in colorectal cancer patients with KRAS-mutated tumors.
"Fewer than half of gastrointestinal cancer patients respond to immune checkpoint inhibitor monotherapy, creating a pressing unmet need for techniques to enhance the efficacy of these agents," Dirk Arnold, director of Asklepios Tumor Center Hamburg and primary investigator of the GOBLET trial, said in a statement. "We believe that pelareorep can address this need and increase the proportion of gastrointestinal cancer patients responding to immune checkpoint inhibitors, as clinical studies have shown that it reverses the immunosuppressive tumor microenvironments underlying checkpoint inhibitor resistance."
Oncolytics, based in Calgary, Alberta, is also studying pelareorep in combination with other drugs. For example, the company has paired pelareorep with Incyte's checkpoint inhibitor retifanlimab in a triple-negative breast cancer trial. In another study involving hormone receptor-positive, HER2-negative breast cancer patients, researchers are exploring the activity of pelareorep with chemotherapy and the checkpoint inhibitor avelumab (Merck KGaA/Pfizer's Bavencio).