A Single Arm, Phase 1/2 Study of SNX-5422 in Subjects With Selected HER2 Positive Cancers.
Heat shock protein 90 (Hsp90) chaperone proteins stabilize well over 200 different known
client proteins helping them to fold correctly as they take up their rightful positions in
the cell. Hsp90 has a special fondness for oncoproteins whose structures shift according to
functional state. Among Hsp90's clients, a surprising number are well recognized targets in
oncology, including human epidermal growth factor receptor 2 (HER2). 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). Treatment of HER2-positive cell lines such as BT-474 with the
Hsp90 inhibitor SNX-2112 results in cellular degradation, decreased levels of
phospho-AKT/cyclin D1, and increased apoptosis. Furthermore, treatment with SNX-5542 caused
tumor regression, including remission in a HER2-overexpressing breast cancer xenograft
model. SNX-5422 has demonstrated significant antitumor activity in mouse xenograft models of
various human malignancies, including breast (BT474, MX-1), lung (H1975, H1650, EBC-1),
colon (HT29), prostate (PC3), and melanoma (A375) with multiple oral dosing regimens.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective Response Rate
The effect of SNX-5422 on tumor progression. Objective tumor responses (complete remissions plus partial remissions) and clinical benefit rate (complete remissions plus partial remissions plus stable disease ≥ 6 months) will be listed by subject. Tumor measurements made using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.Progression free survival and overall survival (time frame: every 3 months until 24 months after the last patient has been enrolled) will be listed by subject.
United States: Food and Drug Administration
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