CYL-02

Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in Western countries, and its incidence has increased over the last 40 years. Curative surgery to manage PDAC is possible in only a fraction of patients; indeed, a vast majority (85%) of patients is diagnosed with locally advanced tumors and/or metastases because they lack specific symptoms and early markers for this disease. For these patients, palliative armamentarium consists of conventional chemotherapeutic agents such as Gemcitabine and, more recently, FOLFIRINOX, which offer marginal survival benefits. Consequently, the prognosis for PDAC is still very poor and there is great need for new treatments that can change this poor outcome. In this context, the investigators have devised, in the past few years, a highly innovative approach based on therapeutic gene transfer, which does not rely on a specific genetic and/or cellular background to inhibit PDAC tumor growth. the investigators found that SSTR2 and DCK::UMK gene transfer demonstrated complementary therapeutic effects to inhibit tumor progression and dissemination, and reduced tumor burden, respectively. On the basis of these promising preclinical data, the investigators conducted past three years the first clinical study of non-viral vector-mediated therapeutic gene delivery, guided by endoscopy (EUS), and combined with standard Gemcitabine therapy in patients with locally advanced and metastatic PDAC. The phase 1 demonstrated that the gene-therapy product CYL-02 is expressed in PDAC tumors (with long-lasting expression within tumor tissues), is distributed within the bloodstream in some extent, when combined with Gemcitabine it can inhibit primary-tumor progression and dissemination. Our results tend to demonstrate therapeutic efficacy, especially in patients with locally advanced tumors. Based on these encouraging results, the investigators propose that patients with locally advanced PDAC at the time of diagnosis may clinically benefit from this approach.
This phase II study is designed to compare the efficacy of intra-tumoral gene delivery of CYL-02 plus Gemcitabine treatment or Gemcitabine alone in patient with locally advanced PDAC.