Mechanism of Action: DNA methyltransferase (DNMT) inhibition
Indication: Treatment-Naïve Acute Myeloid Leukemia (TN-AML)
How this therapy can help
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 inhibits DNMT to reverse aberrant DNA methylation, an epigenetic change characteristic of many cancer cells, restoring the expression of silenced tumor suppressor genes and tumor-associated antigens. Guadecitabine-mediated inhibition of DNA methylation upregulates tumor-associated antigens and may sensitize tumor cells to other anticancer agents, including immunotherapeutics, as well as resensitize 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.
LDAC – low-dose cytarabine; DAC – decitabine; AZA – azacitidine
For more information on clinical studies and status visit: www.clinicaltrials.gov or email: ASTRALfirstname.lastname@example.org.
Previous clinical studies
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.
View all clinical trials with guadecitabine
View Presentations and Publications