First-in-man phase I clinical trial of gene therapy for advanced pancreatic cancer: Safety, biodistribution and preliminary clinical findings.

Buscail L, Bournet B, Vernejoul F, Cambois G, Lulka H, Hanoun N, Dufresne M, Meulle A, Vignolle-Vidoni A, Ligat L, Saint-Laurent N, Pont F, Dejean S, Gayral M, Martins F, Torrisani J, Barbey O, Gross F, Guimbaud R, Otal P, Lopez F, Tiraby G, Cordelier P. – 14/01/2015

Molecular Therapy


This phase I trial was aimed to determine the safety, pharmacokinetics and preliminary clinical activity of CYL-02, a non-viral gene therapy product that sensitizes pancreatic cancer cells to chemotherapy. CYL-02 was administrated using endoscopic ultrasound in twenty-two patients with pancreatic cancer that concomitantly received chemotherapy (gemcitabine). The maximum tolerated dose exceeded the maximal feasible dose of CYL-02 and was not identified. Treatment-related toxicities were mild, without serious adverse events. Pharmacokinetic analysis revealed a dose-dependent increase in CYL-02 DNA exposure in blood and tumors, while therapeutic RNAs were detected in tumors. No objective response was observed, but nine patients showed stable disease up to six months following treatment and two of these patients experienced long term survival. Panels of plasmatic microRNAs and proteins were identified as predictive of gene therapy efficacy. We demonstrate that CYL-02 non viral gene therapy has a favorable safety profile and is well tolerated in patients. We characterize CYL-02 biodistribution and demonstrate therapeutic gene expression in tumors. Treated patients experienced stability of disease and predictive biomarkers of response to treatment were identified. These promising results warrant further evaluation in phase II clinical trial