Study of SNX-5422 in TP53 Null Cancers

Cancer Clinical Trial

Official title: A Single Arm Study of SNX-5422 in Subjects With TP53 Null Cancers

Status Terminated

Clinical Trial Summary

SNX-5422 is a pro-drug of SNX-2112, a potent, highly selective, small-molecule inhibitor of the molecular chaperone heat shock protein 90 (Hsp90). Initial in vitro evidence supports that SNX-5422 may be active against TP53 null tumors irrespective of tumor type .

Clinical Trial Description

The tumor suppressor gene TP53 codes for a central regulator of the DNA-damage-response pathway, and its activation leads to cell-cycle arrest and DNA repair, apoptosis, or senescence through both transcription-dependent and transcriptional-independent activities. Somatic TP53 gene alterations are frequent in most human cancers.

SNX-5422 is a pro-drug of SNX-2112, a potent, highly selective, small-molecule inhibitor of the molecular chaperone heat shock protein 90 (Hsp90). Inhibitors of the chaperone protein Hsp90 are of current interest because of the central role that Hsp90 plays in the maturation and maintenance of numerous proteins that are critical for tumor cell viability and growth.

SNX-2112 retains activity in cell lines with loss of the TP53 gene from one of the alleles. SNX-2112 displays good activity in cell lines with TP53 null/TP53 wild type (e.g., MEC-1 [chronic lymphocytic leukemia]) and TP53 null/TP53 mutation (e.g., EBC-1, NCI-H520 [all NSCLC

• squamous cell carcinoma]). Even in the most extreme case in which TP53 is lost from both alleles, i.e., the cancer cell is totally devoid of the TP53 gene (e.g., H1299, KATO III, HL-60, SK-MES-1), SNX-2112 retains activity

It appears that SNX-2112 could be active against both hematological and solid tumors with a TP53 null status. ;

Related Conditions & MeSH terms

• Cancer

• NCT number: NCT02612285
• Study type: Interventional
• Source: Esanex Inc.
• Status: Terminated
• Phase: Phase 2
• Start date: March 2016
• Completion date: October 2016