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|Ref Type||Journal Article|
|Authors||Pirollo KF, Nemunaitis J, Leung PK, Nunan R, Adams J, Chang EH|
|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.|
|Journal||Molecular therapy : the journal of the American Society of Gene Therapy|
|Abstract Text||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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|SGT-53||transferrin receptor-targeted liposomal p53 cDNA|Synerlip p53||p53 Gene Therapy 4||SGT-53 is a cationic liposomal complex that is linked to an antibody targeting the transferrin receptor (Tff) and contains wild-type Tp53 plasmid, thereby delivering wild-type Tp53 to tumor cells expressing Tff and potentially restoring wild-type Tp53 activity (PMID: 23470564, PMID: 27357628, PMID: 31241175)|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||Advanced Solid Tumor||not applicable||Docetaxel + SGT-53||Phase Ib/II||Actionable||In a Phase Ib trial, the combination of Taxotere (docetaxel) and SGT-53 demonstrated safety, and out of 12 evaluable patients resulted in partial response (PR) in 2 patients, an unverified PR in 1 patient, stable disease with tumor shrinkage in 2 patients, and stable disease without tumor shrinkage in 4 patients with advanced solid tumors (PMID: 27357628).||27357628|