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• W2949968315 abstract "Background: ME-401, a potent and selective oral PI3kδ inhibitor, has demonstrated very high and durable objective response rates (ORR) in both FL and CLL/SL; 76% in 38 patients with relapsed/refractory (R/R) FL and 100% in 12 patients with CLL/SLL (Soumerai 2018, Zelenetz 2018). A continuous dosing schedule resulted in delayed (>cycle 2) grade 3 adverse events of diarrhea and skin rash in ~1/3 of patients, likely related to on-target effects on T-regs resulting in immune-mediated toxicity. Based on the half-life of ME-401 (~26 hours) and the reported kinetics of T-reg regeneration (~10 days) we developed a rational ’intermittent’ dosing schedule of 7 daily doses/28-day cycle after 2 cycles of continuous daily dosing. We hypothesized that such a schedule would provide 10-12 days of effective PI3kδ inhibition followed by washout and sufficient time for T-reg recovery. Preliminary evaluation of this novel schedule resulted in a decrease in delayed Grade 3 immune-related adverse events (irAE's) from 34% to 11%. To define the optimal balance of safety and efficacy of ME-401 in refractory R/R FL, we designed this phase 2 study evaluating 2 dosing schedules. Methods: This is a study of ME-401 in patients with FL after failure of ≥2 prior systemic therapies and will enroll 150 patients. Group A will receive 60mg QD on a continuous schedule until disease progression (PD) or toxicity. Group B will receive 60mg QD on a continuous schedule for 2 cycles then QD for the first 7 days of each subsequent cycle. In this group PD will trigger dose modification to the continuous schedule. Subjects who develop grade ≥2 irAE in A or B will trigger dose modification to open label intermittent schedule. The primary objectives are ORR using Lugano Response Criteria, as determined by an Independent Response Review Committee, and tolerability defined as the rate of AE's requiring dose modification or study drug discontinuation. A correlative study will evaluate the effects of ME-401 on T-cell subsets, cytokines and chemokines. The study opened to enrollment in December 2018 with approximately 80 global sites planned. (NCT03768505) Keywords: follicular lymphoma (FL); PI3K/AKT/mTOR. Disclosures: Zelenetz, A: Consultant Advisory Role: MEI, Amgen, Astra Zeneca, Bayer, BeiGene, Celgene, DAVA oncology, Roche/Genentech, Jannsen, Gilead, Karyopharm, Morphosys, Novartis, Pharmacyclics/Abbvie, Pfizer, Verastem. Zinzani, P: Consultant Advisory Role: MSD, Eusopharma, Verastem, Sanofi (both), ad board only – Celltrion, Janssen-Cilag, Gilead, BMS, Sandos, Servier, Immune design, Celgene, Portolo, Roche, KYOWA KIRIN; Other Remuneration: Speaker: MSD, Eusopharma, Verastem, Celltrion, Janssen-Cilag, Gilead, BMS, Servier, Immune Design, Celgene, Portolo, Roche, KYOWA KIRIN. Buske, C: Honoraria: Roche, Janssen, Pfizer, Celltrion, Hexal; Research Funding: Roche, Janssen, Bayer. Ribrag, V: Consultant Advisory Role: Epizyme, Servier, Nanostring, Gilead, Pharmamar, BMS, MSD, Incyte, Roche, Infinity; Research Funding: Epizyme, ArgenX. Cunningham, D: Research Funding: AstraZeneca, Celgene, MedImmune, Bayer, 4SC, Clovis, Eli Lilly, Janssen, Merck. Jurczak, W: Consultant Advisory Role: Astra Zeneca, Gilead, Sandoz, Novartis, Roche, Morphosys; Research Funding: Morphosys, Roche, Sandoz-Novarttis, Celtrione, Celgene, Janssen, Astra Zeneca, Gilead, TG Therapeutics, Incyte, Bayer. Abrisqueta, P: Consultant Advisory Role: Janssen, Abbvie, Roche; Honoraria: Janssen, Abbvie, Roche; Other Remuneration: Speaker: Janssen, Abbvie, Roche. Wood, J: Employment Leadership Position: MEI Pharma, Inc. Llorin-Sangalang, J: Employment Leadership Position: MEI Pharma, Inc. Brown, J: Consultant Advisory Role: Abbvie, Acerta, Astra Zeneca, BeiGene, Gilead, Invectys, June/Celgene, Kite, Loxo, Pfizer, Morphosys, Novartis, Pharmacyclics, Roche/Genentech, Sunesis, TG Therapeutics, Verastem; Honoraria: Janssen, Teva; Research Funding: Gilead, Loxo, Sun, Verastem." @default.
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• W2949968315 date "2019-06-01" @default.
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• W2949968315 title "A PIVOTAL, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, TWO-ARM, PHASE 2 STUDY OF ME-401 INVESTIGATING TWO DOSING SCHEDULES IN PATIENTS WITH FOLLICULAR LYMPHOMA (FL) AFTER FAILURE OF TWO OR MORE PRIOR SYSTEMIC THERAPIES" @default.
• W2949968315 doi "https://doi.org/10.1002/hon.2_2632" @default.
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