Guadecitabine was rationally designed to prolong the exposure of tumor cells to the active metabolite, decitabine, ensuring greater uptake of decitabine into the DNA of rapidly dividing cancer cells.
As a next generation DNA-hypomethylating agent, guadecitabine targets and reverses aberrant DNA hypermethylation, an epigenetic change characteristic of many cancer cells, restoring the expression of silenced tumor suppressor genes and cancer testis antigens. Guadecitabine-mediated demethylation of DNA upregulates tumor-associated antigens, and may sensitize tumor cells to other anticancer agents, including immunotherapeutics, as well as resensitizing resistant cancer cells to chemotherapeutics.
Astex is conducting ASTRAL-1 (Treatment Naïve AML): 800-patient multicenter, randomized, open-label study of SGI-110 versus treatment choice (TC) in adults with previously untreated Acute Myeloid Leukemia (AML) who are not considered candidates for intensive remission induction chemotherapy.
The ASTRAL-1 clinical study is based on data from a completed 400-patient Phase 1/2 study of guadecitabine in patients with AML or MDS (www.clinicaltrials.gov).
Other active clinical programs
Astex also has an active program evaluating the combination of guadecitabine with checkpoint inhibitors in the treatment of both hematological malignancies and solid tumors, and as a single agent and in combination with chemotherapy for the treatment of solid tumors. These include studies investigating combination with carboplatin in the treatment of platinum-resistant ovarian cancer; in hepatocellular (liver) cancer following failure of Nexavar® (sorafenib), and in combination with irinotecan in the treatment of colorectal cancer.