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|Ref Type||Journal Article|
|Authors||Mahalingam D, Goel S, Aparo S, Patel Arora S, Noronha N, Tran H, Chakrabarty R, Selvaggi G, Gutierrez A, Coffey M, Nawrocki ST, Nuovo G, Mita MM|
|Title||A Phase II Study of Pelareorep (REOLYSIN®) in Combination with Gemcitabine for Patients with Advanced Pancreatic Adenocarcinoma.|
|Date||2018 May 25|
|Abstract Text||Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with 1 and 5-year survival rates of ~18% and 7% respectively. FOLFIRINOX or gemcitabine in combination with nab-paclitaxel are standard treatment options for metastatic disease. However, both regimens are more toxic than gemcitabine alone. Pelareorep (REOLYSIN®), a proprietary isolate of reovirus Type 3 Dearing, has shown antitumor activity in clinical and preclinical models. In addition to direct cytotoxic effects, pelareorep can trigger antitumor immune responses. Due to the high frequency of RAS mutations in PDAC, we hypothesized that pelareorep would promote selective reovirus replication in pancreatic tumors and enhance the anticancer activity of gemcitabine. Chemotherapy-naïve patients with advanced PDAC were eligible for the study. The primary objective was Clinical Benefit Rate (complete response (CR) + partial response (PR) + stable disease (SD) ≥ 12 weeks) and secondary objectives include overall survival (OS), toxicity, and pharmacodynamics (PD) analysis. The study enrolled 34 patients; results included one partial response, 23 stable disease, and 5 progressive disease. The median OS was 10.2 months, with a 1- and 2-year survival rate of 45% and 24%, respectively. The treatment was well tolerated with manageable nonhematological toxicities. PD analysis revealed reovirus replication within pancreatic tumor and associated apoptosis. Upregulation of immune checkpoint marker PD-L1 suggests future consideration of combining oncolytic virus therapy with anti-PD-L1 inhibitors. We conclude that pelareorep complements single agent gemcitabine in PDAC.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Pelareorep + Pembrolizumab||Pelareorep Pembrolizumab||0||1|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Pelareorep||REOLYSIN||RAS Inhibitor (Pan) 8||Reolysin (Pelareorep) is a reovirus, which specifically infects and replicates in RAS-activated cells to induce apoptosis, and may also induce anti-tumor immune response (PMID: 29799479).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||pancreatic ductal adenocarcinoma||not applicable||Gemcitabine + Pelareorep||Phase II||Actionable||In a Phase II trial, Reolysin (pelareorep) in combination with Gemzar (gemcitabine) resulted in partial response in 3% (1/34), stable disease in 68% (23/34) of patients with advanced pancreatic ductal adenocarcinoma, with a median overall survival of 10.2 months, and a 1- and 2-year survival rate of 45% and 24% respectively (PMID: 29799479).||29799479|