Entries by Renee Hansen

2017 EORTC: Phase 1 study of the IAP inhibitor ASTX660 in adults with advanced cancers and lymphomas

Summary Due to their roles in the evasion of apoptosis, Inhibitor of Apoptosis Proteins (IAPs) are considered attractive targets for anti-cancer therapy. ASTX660 is a potent, next generation, non-peptidomimetic, dual antagonist of both XIAP and cIAP1, discovered using fragment-based drug design (1-3). We report here the results of the first-in-human phase 1 dose escalation and […]

2017 ESH-AML: LINE-1 and P15 Demethylation May Predict Response to Guadecitabine

Summary Guadecitabine (formerly known as SGI-110) is a next-generation hypomethylating agent (HMA) composed of a dinucleotide of decitabine and deoxyguanosine (Figure 1). Guadecitabine is a dinucleotide resistant to degradation by cytidine deaminase (CDA) resulting in longer in vivo exposure to its active metabolite, decitabine, after a small volume ( ~ 1 mL) subcutaneous (SC) administration. […]

2017 ACCP: Population Pharmacokinetics Analysis for Guadecitabine (SGI-110) and Decitabine after Subcutaneous Dosing with SGI-110 in Patients with Relapsed/Refractory AML and MDS

Summary Guadecitabine is next-generation HMA formulated as a dinucleotide of decitabine and deoxyguanosine delivered as a low volume and pharmaceutically stable subcutaneous (SC) injection. In vivo conversion to active metabolite decitabine results in longer effective half-life and more extended decitabine exposure window than decitabine IV infusion. The differentiated PK profile may lead to improved biological […]

2017 EHA: DOSE-CONFIRMATION STUDY OF ORAL ASTX727, A COMBINATION OF ORAL DECITABINE WITH A CYTIDINE DEAMINASE INHIBITOR (CDAI) E7727, IN SUBJECTS WITH MYELODYSPLASTIC SYNDROMES (MDS): PRELIMINARY RESULTS

Summary An oral hypomethylatingagent which could be administered in a dose which would emulate parenteral pharmacokinetics would be more convenient and potentially enhance adherence to treatment. Heretofore, rapid clearance by cytidine deaminase (CDA) during first pass has prevented oral administration.1E7727, a novel CDAi, is orally bioavailable with a large safety margin and reproducible effectiveness in […]

2017 14th Intl. Symposium on MDS: Randomized Phase 2 Study of Guadecitabine in Patients with HMA-Naïve Higher Risk Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML)

Summary Guadecitabine (formerly SGI-110) is a next generation subcutaneous (SC) small volume dinucleotide HMA which results in prolonged in vivo exposure to active metabolite decitabine, and clinical activity reported in phase 1 in MDS and AML patients (Issa et al, Lancet Oncology 2015). View further details below 2017 14th Int. Symposium in MDS: Randomized Phase […]

2017 ASCPT: Development of a Semi-Mechanistic PK/PD Model of an Oral Fixed Dose Combination (FDC) of Cytidine Deaminase Inhibitor E7727 with Decitabine (ASTX727) in Subjects with Myelodysplastic Syndromes.

Summary ASTX727 is an oral Fixed Dose Combination of a novel and potent oral CDA inhibitor, E7727 with decitabine for the treatment of patients with MDS. Decitabine is an approved IV treatment of MDS that is rapidly degraded by cytidine deaminase resulting in poor and variable oral bioavailability. Low doses of oral decitabine co-administered with […]

2016 ASH: Successful Emulation of IV Decitabine Pharmacokinetics with an Oral Fixed-Dose Combination of the Oral Cytidine Deaminase Inhibitor (CDAi) E7727 with Oral Decitabine, in Subjects with Myelodysplastic Syndromes (MDS): Final Data of Phase 1 Study

Summary Patients with International Prognostic Scoring System (IPSS) intermediate 1 and 2 (Int) and high risk (HR) MOS benefit from therapy with hypomethylating agents (HMAs) decitabine (DAC) and azacitidine (AZA). Treatment requires 5 or 7 daily parenteral doses every month while the patient is benefitting. An oral HMA taken at home would provide patient convenience, […]

2016 ASH: Genetic Determinants of Response to Guadecitabine (SGI-110) in AML

Summary Guadecitabine is a next generation hypomethylating drug with improved pharmacokinetics and pharmacodynamics compared to decitabine and demonstrated clinical activity in both treatment naïve (tn) and relapsed-refractory (rr) AML. Previous studies reported similar response rates to guadecitabine in different cytogenetic subsets but it remains unknown whether this extends to genetic changes. View further details below […]

2016 ASH: Long Term Survival and Clinical Complete Responses of Various Prognostic Subgroups in 103 Relapsed/Refractory Acute Myeloid Leukemia (r/r AML) Patients Treated with Guadecitabine (SGI-110) in Phase 2 Studies

Summary Guadecitabine (SGI-110) is a novel next-generation hypomethylating agent (HMA) administered as a small volume subcutaneous (SC) injection which results in extended decitabine exposure. Phase 2 study has been conducted in r/r AML patients using two different doses and schedules of guadecitabine. We report here long term survival and clinical complete response rates in various […]