A phase I study of duvelisib in combination with oral azacitidine (CC-486) in relapsed lymphoid malignancies.

• DOI: 10.1200/jco.2022.40.16_suppl.tps7594
• Publication Date: 2022-06-06T16:57:52Z
• Authors: Hayder Saeed; Eva Sahakian; Kamira Karen Maharaj; Qianxing Mo; Ling Zhang; Rikesh J Makanji; Leidy Lismeri Ise...; Sameh Gaballa; Julio C. Chavez; Bijal D. Shah; Celeste M. Bello; Javier Pinilla-Ibarz; Lubomir Sokol
• Keywords: Azacitidine; T-Cell Lymphoma

TPS7594 Background: Phosphoinositide 3-kinase (PI3K) inhibitors have shown promising activity in lymphoid malignancies such as mature T cell lymphoma, diffuse large B and mantle lymphoma. Duvelisib’s PI3K-δ PI3K-γ lymphoma is a single agent (Horwitz, Koch et al. 2018). While the safety profile can generally be managed, certain autoimmune adverse events may limit its adaptation clinical practice. Azacitidine, pyrimidine nucleoside analog of cytidine, active (Saillard, Guermouche 2017) well DLBCL (Martin, Bartlett Hypomethylators could enhance PI3K through increasing PTEN expression (Spangle, Roberts 2017), upregulation tumor suppressor genes (Zuo, Liu 2011). immune mediated related to shifts differentiation towards Th17 phenotype decreases reg that found more pronounced patients with higher toxicity (Gadi, Kasar 2019). Studies regs induced from Cd4+CD25- cells using DNA methyltransferase inhibition azacitidine (Fagone, Mazzon Thus, intermittent administration azacytidine potentially restore balance by decrease while maintaining enhances killing myelodysplastic syndrome (Jia, Yang 2020). Methods: This 3+3 phase I dose escalation study designed determine maximum tolerated (MTD) CC-486 combination duvelisib malignancies. The MTD defined highest an observed incidence limiting (DLT) no than one out six treated at particular level. Secondary endpoints include best overall response, disease control rate duration response. Exploratory end points will biomarker driven focus on composition different compartments during combination. Efficacy biomarkers measuring phosphorylation AKT peripheral CD3+ cells. Oral given continuously maintained first 2 cycles schedule 14 days on/14 off. cohort are enrolled, DLT testing period. Clinical trial information: NCT05065866.