Phase II trial of pexa-vec (pexastimogene devacirepvec; JX-594), an oncolytic and immunotherapeutic vaccinia virus, in patients with metastatic, refractory renal cell carcinoma (RCC).

Abstract

671 Background: Pexa-Vec is a vaccinia virus engineered to express granulocyte-macrophage colony stimulating factor (GM-CSF), thereby stimulating anti-tumor immunity, direct oncolysis, and tumor vascular disruption. ( Nat Rev Cancer 2009). Pexa-Vec was shown to replicate in metastatic tumors following intratumoral (IT) or intravenous (IV) administration ( Lancet Oncol 2008; Nature 2011). Methods: RCC patients failing at least 1 prior VEGF/R-targeted therapy received five weekly IV Pexa-Vec infusions. Starting at Week 6, patients with disease control or otherwise clinically benefitting from treatment could continue to receive IV infusions every 3 weeks. The primary study objective was radiographic response based on modified Response Evaluation Criteria (RECIST) 1.0. Secondary objectives included disease control rate, progression free survival and safety. Results: All seventeen patients enrolled received the initial 5 weekly Pexa-Vec infusions. Twelve patients received at least one additional infusion (median Pexa-Vec infusions = 8; range 5-12). The treatment regimen was well-tolerated. Transient influenza-like illness (100%), asthenia (47%), anemia (29%) and nausea (29%) were the most common adverse events. All patients were evaluable radiographically at Week 6. The RECIST disease control rate was 76% at Week 6 including 1 complete response. Conclusions: Pexa-Vec was well-tolerated and associated with one complete RECIST response and 76% disease control at Week 6 in patients with advanced RCC. Further trials of Pexa-Vec in RCC patients are warranted.

Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes

“…Pexa-Vec Phase II trial in patients with metastatic refractory renal cell carcinoma who failed at least one prior VEGF/R-targeted therapy demonstrated a 76% RECIST disease control rate at Week 6 including one complete response [ 85 ].…”

Oncolytic Vaccinia Virus Expressing White-Spotted Charr Lectin Regulates Antiviral Response in Tumor Cells and Inhibits Tumor Growth In Vitro and In Vivo

“…Vaccinia viruses can be used as replicating vectors harboring therapeutic genes to directly lyse tumor cells, or as cancer vaccines to stimulate antitumor immunity [ 10 , 11 , 12 ]. JX-594, the most famous oncolytic vaccinia virus carrying a human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene with the thymidine kinase (TK) gene deletion, has been advanced to clinical phase III for the treatment of advanced hepatocellular carcinoma (HCC) and clinical phase II trial for renal cell carcinoma [ 13 , 14 , 15 , 16 , 17 ]. In our previous work, genes encoding marine lectins Tachypleus tridentatus lectin (TTL) and Aphrocallistes vastus lectin (AVL) were inserted into the oncolytic vaccinia virus (oncoVV) vector, forming oncoVV-TTL and oncoVV-AVL recombinant viruses, respectively [ 18 , 19 ].…”

Quantitative Proteome Responses to Oncolytic Reovirus in GM-CSF- and M-CSF-Differentiated Bone Marrow-Derived Cells

“…Of note, the use of GM-CSF in combination with reovirus and other oncolytic viruses has been shown to enhance antitumor immunity. Indeed, the FDA-approved OV T-VEC (and other OV formulations like Pexa-Vec) has been genetically modified to overexpress GM-CSF. − …”