On May 20, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported clinical and biomarker data demonstrating clinical proof-of-concept for pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer (Press release, Oncolytics Biotech, MAY 20, 2021, View Source [SID1234580368]). The data will be featured in an upcoming electronic poster presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is taking place virtually from June 4 – 8, 2021.
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The newly announced data are from a phase 2 trial evaluating pelareorep in combination with the PD-1 inhibitor pembrolizumab (KEYTRUDA) in pancreatic adenocarcinoma patients who progressed after first-line treatment. Findings from the trial indicate that pelareorep and pembrolizumab synergize and show anti-cancer activity in these difficult-to-treat patients, which is mediated through the complementary immunotherapeutic effects of the two agents.
"These results are very promising, particularly considering the extremely challenging patient population enrolled in the trial. That we saw a response signal in select patients, despite the absence of chemotherapy, provides evidence of the considerable anti-cancer activity of pelareorep-pembrolizumab combination therapy," said Principal Investigator, Devalingam Mahalingam, M.D., Ph.D., Associate Professor of Medicine at The Northwestern University Feinberg School of Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "We notably observed an association between treatment-induced anti-cancer immune responses and improved tumor control in some patients, which demonstrates pelareorep’s underlying immunologic mechanism of action and validates the strategy of combining it with checkpoint inhibition. I look forward to discussing these data with the scientific community at the upcoming ASCO (Free ASCO Whitepaper) conference and to the continued evaluation of pelareorep-checkpoint inhibitor combination therapy in select patients with pancreatic and other gastrointestinal cancers."
The data presented in the upcoming ASCO (Free ASCO Whitepaper) poster represent an update based on additional data that was collected after the cutoff date used for the poster’s corresponding abstract. Key data and conclusions that will be featured in this upcoming poster include:
Disease control was achieved in 42% (5/12) of patients, with one patient achieving a partial response and four patients achieving stable disease
On-treatment tumor biopsies showed pelareorep replication and increased infiltration of CD8+ T cells and PD-L1+ cells relative to pre-treatment samples
Patients achieving disease control showed reductions in pro-tumor regulatory T (Treg) cells in the peripheral blood and tumor tissue compared to those with progressive disease
Patients achieving disease control showed increased activation of anti-cancer CD8+ T cells in the peripheral blood compared to those with progressive disease
Pelareorep-pembrolizumab combination therapy was found to be well tolerated, with most treatment-related adverse events being grade 1 or 2
Bin Zhang, M.D., Ph.D., Professor at The Northwestern University Feinberg School of Medicine, commented, "These data show that pelareorep can train the immune system to target pancreatic cancer while simultaneously promoting the infiltration of T cells into the tumor and remodeling the tumor microenvironments (TMEs) to be less immunosuppressive. This positions pelareorep to synergistically combine with both checkpoint inhibitors as well as a broad range of other immuno-oncology agents."
"The findings from this study highlight the broad applicability of pelareorep’s immunotherapeutic mechanism of action as they are consistent with what has been seen in clinical trials in other indications such as breast cancer," added Thomas Heineman, M.D., Ph.D., Global Head of Clinical Development and Operations at Oncolytics. "The compelling findings from this phase 2 study highlight the potential of pelareorep to address the critical unmet need in pancreatic cancer by reversing the immunosuppressive TMEs that often limit the efficacy of checkpoint inhibitors. The anti-cancer activity demonstrated in this study bodes well for a successful outcome in our GOBLET trial, which includes a cohort evaluating pelareorep and the PD-L1 inhibitor atezolizumab in combination with chemotherapy as first-line therapy in metastatic pancreatic cancer patients."
The electronic poster, titled, "Treatment with pembrolizumab in combination with the oncolytic virus pelareorep promotes anti-tumor immunity in patients with advanced pancreatic adenocarcinoma" will be made available on the ASCO (Free ASCO Whitepaper) Annual Meeting website at 9:00 a.m. ET on June 4, 2021. A copy of the poster will also be posted on the Posters & Publications page of Oncolytics’ website (LINK).
Oncolytics plans to further develop pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer in collaboration with Roche and AIO-Studien-gGmbH (AIO) through the GOBLET study, a phase 1/2 multi-center trial designed to investigate the use of pelareorep in combination with Roche’s anti-PD-L1 inhibitor atezolizumab (Tecentriq) in patients with metastatic pancreatic, metastatic colorectal and advanced anal cancers (link to the GOBLET announcement PR). Oncolytics expects the first patient to be dosed in GOBLET in mid-2021.
About GOBLET
The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication biomarker, safety, and efficacy study in advanced or metastatic GI tumors. The study will be conducted at 25 centers in Germany. The primary endpoint of the study is safety, with overall response rate and biomarker evaluation (T cell clonality and CEACAM6) as exploratory endpoints. Approximately 55 patients are planned for enrollment across four separate cohorts:
Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line metastatic pancreatic cancer patients (n=12);
Pelareorep in combination with atezolizumab in 2nd and 3rd line metastatic colorectal cancer patients that are diagnosed as MSI (microsatellite instability) high (n=19);
Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients (n=14); and
Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients (n=10).
About Gastrointestinal Cancer
Excluding skin cancers, colorectal cancer is the third most common cancer, with an estimated 104,610 new cases of colon cancer and 43,340 new cases of rectal cancer diagnosed in the U.S. in 20201. Also, for the 2020 year, the American Cancer Society estimates there will be 57,600 new cases of pancreatic cancer2 and 8,590 new cases of anal cancer 3 in the U.S.