A Phase 0/1 Study of cDNA for TP53, Checkpoint Inhibition and Radiation in Children With Recurrent, Progressive or Refractory CNS Malignancies.

SGT-53 is a novel cationic liposome encapsulating a normal human wild type TP53 cDNA sequence in a plasmid backbone. The liposome is decorated on its surface with an anti- transferrin receptor (TfR) single chain antibody fragment (scFv) that is designed to target cancer cells through the binding of the TfRscFv to the transferrin receptor. This complex has been shown to efficiently and specifically deliver the TP53 complementary DNA (cDNA) to the tumor cells via receptor-mediated endocytosis of the cationic liposomal complex. Introduction of the TP53 cDNA sequence restores wild-type p53 (wtp53) function in the apoptotic pathway.

Re-irradiation has rapidly grown into a primary consideration in the context of recurrent pediatric CNS malignancies. While not thought to be curative by itself, it has often resulted in temporary symptomatic improvement as well as occasional radiographic regression or stabilization, although as with any irradiation, may also cause some adverse events.

Given the poor prognosis for children with recurrent CNS malignancies and the importance of p53 function in these tumors, we propose a pilot study of SGT-53 in combination with re-irradiation and checkpoint inhibition followed by maintenance therapy with SGT-53 in combination with nivolumab to evaluate the safety, feasibility and preliminary efficacy. SGT-53 will be added to a salvage regimen utilized in patients with recurrent tumors of re- irradiation and nivolumab followed by combination therapy with SGT-53 and nivolumab.