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Oncolytic Virus Therapy Shows Promise in Patients With Pancreatic Cancer
Final results from a phase II trial of Reolysin (Oncolytics Biotech Inc.) in combination with gemcitabine (Gemzar, Eli Lilly) in patients with advanced pancreatic cancer have been presented at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer.
Reolysin is a proprietary variant of the reovirus (an acronym for “respiratory enteric orphan virus”), which is widely found in the environment. By adulthood, most people have been exposed to the reovirus. The reovirus is nonpathogenic, which means that infections are typically asymptomatic. In clinical trials, Reolysin was well-tolerated, with patients exhibiting only mild, flu-like symptoms. Reolysin has been used alone and in combination with chemotherapy and radiotherapy for various cancers.
Research found that the reovirus was able to infect and selectively destroy cancer cells. When a normal cell is infected with the reovirus, an antiviral response is activated, which prevents the virus from replicating within the cell. However, inside a cancer cell with one or more mutations on a growth pathway called the Ras pathway, there is an aberrant antiviral response that is unable to prevent the virus from replicating. This abnormality allows the reovirus to multiply to an extent that is fatal to the cancer cell.
The REO 017 trial was a single-arm study of intravenous (IV) Reolysin in combination with gemcitabine in chemotherapy-naïve patients with advanced or metastatic pancreatic cancer. Eligible patients were treated with gemcitabine (800 mg/m2 on days 1 and 8) and Reolysin (1 × 1010 TCID50 administered IV on days 1, 2, 8, and 9 every 3 weeks). A tumor assessment was performed every two cycles. The trial enrolled 33 evaluable patients using a two-stage design. In the first stage, 17 patients were enrolled, and the best response was noted. If three or more responses (defined as a complete response [CR], a partial response [PR], or stable disease [SD]) were observed among the 17 patients, the study enrolled an additional 16 patients, for a total of at least 33 evaluable subjects. This initial endpoint was met after six evaluable patients were enrolled. The study’s primary objective was to determine the clinical benefit rate (CBR) of multiple IV doses of Reolysin in combination with gemcitabine in patients with advanced or metastatic pancreatic cancer. The secondary objectives were to determine progression-free survival (PFS) as well as the safety and tolerability of Reolysin when administered in combination with gemcitabine.
A survival analysis of 33 patients showed median PFS of 4.0 months and median overall survival (OS) of 10.2 months. In comparison, the ACCORD 11 trial of gemcitabine alone had median PFS of 3.3 months and OS of 6.8 months. Further, in the MPACT trial of gemcitabine, median PFS was 3.7 months and OS was 6.6 months.
The new data also showed 1- and 2-year survival rates of 45% and 24%, respectively, for Reolysin plus gemcitabine. In the ACCORD 11 trial, the 1- and 2-year survival rates were 20% and 2%, respectively, and in the MPACT trial they were 22% and 5%.
The investigators found up-regulation of programmed death ligand 1 (PD-L1), an immune checkpoint marker, in post-treatment tumors, suggesting the potential to combine oncolytic viral therapy with anti–PD-L1 inhibitors in future trials.
Of the 29 patients who were evaluable for clinical response, one patient had a PR; 23 had SD; and five had progressive disease as their best response. This translated into a CBR (CR + PR + SD) of 83%.