- Clinical Pipeline
- Guadecitabine (SGI-110) DNMT inhibitor (Hematological Malignancies and Solid Tumors)
- ASTX029 Extracellular Signal-Related Protein Kinases (ERK 1/2) Inhibitor (Solid Tumors)
- Oral Decitabine and Cedazuridine (ASTX727) (Hematological Malignancies)
- ASTX660 Dual IAP Antagonist (Solid Tumors & Lymphomas)
- ASTX295 Oral Murine Double Minute 2 (MDM2) antagonist (Solid Tumors)
- Partnered Products and Programs
- Kisqali®(ribociclib) CDK4/6 inhibitor (Oncology)
- Balversa® (erdafitinib) FGFr inhibitor (Oncology)
- AZD5363 PKB/Akt Inhibitor (Oncology)
- Multiple Targets and Therapeutic Areas
- Pyramid™ Discovery Platform
- Oncology and CNS Discovery
- Sustaining Innovation
| Phase 1 | Phase 2 | Phase 3 |
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Guadecitabine (SGI-110)
DNMT inhibitor (Hematological Malignancies and Solid Tumors)
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Ownership: Astex
Mechanism of Action: DNA methyltransferase (DNMT) inhibition
Indications: Relapsed/Refractory Acute Myeloid Leukemia (AML), Relapsed/Refractory Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukaemia (CMML)
How this therapy can help
Guadecitabine was rationally designed to be resistant to degradation by cytidine deaminase and 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.
Clinical studies
Astex is conducting the ASTRAL-2 and ASTRAL-3 Global Phase 3 clinical studies with guadecitabine.
ASTRAL-2 (Relapsed/Refractory AML): 404-patient multicenter, randomized, open-label study of Acute Myeloid Leukemia (AML) patients who failed or relapsed following prior intensive chemotherapy.
HiDAC- high-dose cytarabine; MEC – mitoxantrone, etoposide, cytarabine; FLAG±Ida – fludarabine, cytarabine, G-CSF, ± idarubicin; LDAC – low-dose cytarabine; DAC – decitabine; AZA – azacitidine; BSC – best supportive care
ASTRAL-3 (Relapsed/Refractory MDS or CMML): 408-patient multicenter, randomized, open-label study in Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML) after failure of prior azacitidine, decitabine, or both.
LDAC – low-dose cytarabine; IC (7+3) – intensive chemotherapy (cytarabine/anthracycline); BSC – best supportive care
For more information on clinical studies and status visit: www.clinicaltrials.gov or email: ASTRAL-2@astx.com or ASTRAL-3@astx.com.
Previous clinical studies
The ASTRAL-2 and ASTRAL-3 clinical studies are based on data from a completed 400-patient Phase 1/2 study of guadecitabine in patients with AML or MDS (www.clinicaltrials.gov).
Astex has also completed the ASTRAL-1 Phase 3 clinical study:
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 results from this study were presented at the Annual Meeting of the European Hematology Association in June 2019.
LDAC – low-dose cytarabine; DAC – decitabine; AZA – azacitidine
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. Astex has also completed studies investigating combination with carboplatin in the treatment of platinum-resistant ovarian cancer and in hepatocellular (liver) cancer following failure of Nexavar® (sorafenib).