December 30, 2020 - The phase 1/2 GOBLET trial will investigate the use of pelareorep in combination with atezolizumab in patients with metastatic colorectal and advanced or metastatic pancreatic and anal cancers.
Thomas C. Heineman, MD, PhD
Oncolytics Biotech and Roche are launching a new study for multi-indication gastrointestinal (GI) cancer in Germany. The phase 1/2 trial, known as GOBLET, will investigate the use of pelareorep, in combination with Roche's anti-PD-L1 checkpoint inhibitor atezolizumab (Tecentriq), in patients with metastatic colorectal and advanced or metastatic pancreatic and anal cancers.1
Pelareorep is an intravenous therapy that uses an isolate of a double-stranded RNA virus called reovirus that is found in stagnant water and sewage. This virus can penetrate noncancer cells but is unable to replicate in normal cells. In cancer cells, the compound induces selective tumor lysis and promotes an inflamed tumor phenotype by inducing innate and adaptive immune responses.
“An important attribute of pelareorep is that it can be given intravenously,” Thomas C. Heineman, MD, PhD, global head of clinical development and operations at Oncolytics Biotech, told OncLive. “Most oncolytic viruses are given intratumorally. The ability to give pelareorep intravenously has the obvious benefit of convenience, but it also allows the virus to target metastatic sites that may not be accessible by intratumoral injection. Also, should future studies indicate the need, intravenous administration makes it much easier to provide booster courses of therapy compared with intratumoral administration."
Enrollment in the GOBLET trial (which is not yet listed on ClinicalTrials.gov) is planned to begin in the first half of 2021, Heineman said.
The study will be conducted at multiple centers in Germany and will be managed by AIO, an academic cooperative medical oncology group based in Germany. “If this study shows promising results, then I anticipate that we would move into controlled studies to confirm any clinical benefit, and I expect those would be multinational studies that include the United States. I would anticipate that those studies would be multinational studies that would include North America and the United States,” Heineman said.
The primary end point of the study is safety, with overall response rate and blood-based biomarkers (T cell clonality and CEACAM6) as exploratory endpoints. About 55 patients are planned for enrollment across 4 separate cohorts.
Two cohorts will be with patients with colorectal cancer. In 1 cohort, 14 patients with third-line metastatic colorectal cancer will receive pelareorep in combination with atezolizumab and TAS-102 (trifluridine/tipiracil; Lonsurf). Another cohort will recruit 19 patients with first-line microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer to receive pelareorep in combination with atezolizumab.
A third cohort will recruit 12 patients with metastatic pancreatic cancer for first-line treatment with pelareorep in combination with atezolizumab, gemcitabine (Gemzar), and nab-paclitaxel (Abraxane). A fourth cohort will enroll 10 patients with advanced and unresectable anal cancer for second-line treatment with pelareorep in combination with atezolizumab.
“This is a small study designed to identify a signal, so the cohort sizes range from 10 to 19 patients to allow statistical comparison to historical data,” Heineman said. “In any of the cohorts, if prespecified criteria are met for tumor response and there are no safety issues or concerns, we’ll expand to larger cohorts to better define the efficacy signal.”
The GOBLET study builds on an earlier trial showing that pelareorep-based combination treatments stimulated an adaptive immune response in patients with KRAS mutated colorectal cancer.2,3
In that study, pelareorep was combined with bevacizumab (Avastin) and the chemotherapy regimen of FOLFIRI, which consists of folinic acid, fluorouracil, and irinotecan. The study enrolled 36 patients with KRAS mutation in a dose-escalation trial. The combination was well-tolerated, with promising signals of efficacy. Among 30 evaluable patients, 6 (20%) had a partial response (PR) and 22 patients (73.3%) had stable disease (SD) as their best response, for a clinical benefit rate (PR +SD) of 93.3%. Adverse events included myelosuppression, fatigue, and diarrhea.
Another previous study identified CEACAM6 as a prospective biomarker for pelareorep in the treatment of patients with pancreatic cancer.4
Heineman said the GOBLET and future studies will continue to look for biomarkers that identify populations of patients in any or all of these cohorts that may benefit from treatment with pelareorep plus checkpoint inhibitors.