Phase 2 Trial of Pexa-Vec (pexastimogene devacirepvec; JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus, in Patients with Metastatic, Refractory Renal Cell Carcinoma (RCC)

Background: Pexa-Vec is a vaccinia virus engineered to express granulocyte-macrophage colony stimulating factor (GM-CSF), thereby stimulating direct oncolysis, tumor vascular disruption and anti-tumor immunity (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: Treatment-refractory RCC patients received five weekly intravenous Pexa-Vec infusions. Starting at Week 6, patients exhibiting disease control or otherwise clinically benefitting from Pexa-Vec treatment could continue to receive IV Pexa-Vec infusions every 3 weeks. The primary objective of the study was to determine the radiographic response rate based on modified Response Evaluation Criteria in Solid tumors (RECIST) 1.0. Secondary objectives include disease control rate, progression free survival and safety.
Results: Seventeen (17) RCC patients having failed at least one prior VEGF/R-targeted therapy were enrolled. All patients received the initial 5 weekly Pexa-Vec infusions. Twelve patients (71%) went on to receive at least one additional infusion (median Pexa-Vec infusions = 8; range 5-12). The treatment regimen was well-tolerated. Transient influenza-like illness (n=17; 100%), asthenia (n=8; 47%), anemia (n=5; 29%) and nausea (n=5; 29%) were the most common adverse events. All patients were evaluable radiographically at Week 6. The RECIST response rate was 6% (1 partial response which was classified as a complete response at Week 36). The RECIST disease control rate was 76% at Week 6.
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.