title: Safety and Efficacy in Advanced Solid Tumors of a Targeted Nanocomplex Carrying the p53 Gene Used in Combination with Docetaxel: A Phase 1b Study.
abstract: Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, occurs in most human cancers. SGT-53 is a liposomal nanocomplex designed for systemic, tumor-targeting delivery of the wt p53 gene. In this nanodelivery system, an anti-transferrin receptor single-chain antibody fragment serves as the targeting moiety. In an initial phase 1 trial in patients with advanced solid tumors, SGT-53 demonstrated tumor-specific targeting, was shown to be well tolerated, and was associated with an antitumor effect in several patients. Our preclinical studies have also demonstrated enhanced antitumor activity with the combination of SGT-53 and docetaxel. Thus, this dose-escalation trial was undertaken to assess the combination of SGT-53 and docetaxel for safety and potential efficacy in 14 advanced cancer patients. Results reveal that the combination of SGT-53 (maximum dose, 3.6 mg DNA/infusion) and docetaxel (75 mg/m(2)/infusion) was well tolerated. Moreover, clinical activity involving 12 evaluable patients was observed. Three of these patients achieved RECIST-verified partial responses with tumor reductions of -47%, -51%, and -79%. Two others had stable disease with significant shrinkage (-25% and -16%). These results support phase 2 testing of SGT-53 in combination with docetaxel.
authors.affiliation: Department of Oncology, Experimental Therapeutics Division, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Pirollo
authors.affiliation: Mary Crowley Cancer Research Centers, Dallas, Texas, USA.|Gradalis, Dallas, Texas, USA.|Texas Oncology PA, Dallas, Texas, USA.|Medical City Dallas Hospital, Dallas, Texas, USA.
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.affiliation: SynerGene Therapeutics, Potomac, Maryland, USA.
authors.forename: Po Ki
authors.initials: PK
authors.lastname: Leung
authors.affiliation: Mary Crowley Cancer Research Centers, Dallas, Texas, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Nunan
authors.affiliation: Mary Crowley Cancer Research Centers, Dallas, Texas, USA.
authors.forename: Jana
authors.initials: J
authors.lastname: Adams
authors.affiliation: Department of Oncology, Experimental Therapeutics Division, Georgetown University Medical Center, Washington, District of Columbia, USA.|SynerGene Therapeutics, Potomac, Maryland, USA.
authors.forename: Esther H
authors.initials: EH
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003131:Combined Modality Therapy; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D016158:Genes, p53; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D019233:Retreatment; D043823:Taxoids / Q000008:administration & dosage*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel