AML-328 Phase 2 Study of ASTX727 (Decitabine/Cedazuridine) Plus Venetoclax in Patients With Relapsed/Refractory Acute Myeloid Leukemia or Previously Untreated, Older Adult Patients Unfit for Chemotherapy

Tareq Abuasab, Yesid Alvarado, Ghayas Issa, Rabiul Islam, Nicholas James, Musa Yilmaz, Nitin Jain, Lucia Masarova, Steven Kornblau, Elias Jabbour, Naveen Pemmaraju, Guillermo Montalban Bravo, Sherry Pierce, Courtney DiNardo, Tapan Kadia, Naval Daver, Marina Konopleva, Guillermo Garcia-Manero, Farhad Ravandi

Research output: Contribution to journalArticlepeer-review

Abstract

Context: ASTX727 is an oral formulation of the fixed-dose combination of decitabine and cedazuridine (100 mg/35 mg). Objective: To investigate whether a total oral regimen of ASTX727+venetoclax (ven) is feasible and safe. Methods: Pts ≥18 with relapsed/refractory AML (R/R) or pts with AML aged ≥75 or 18–74 unfit for intensive chemotherapy (frontline; FL) were eligible. Other eligibility criteria included adequate renal and hepatic function and ECOG performance status (PS) ≤2. ASTX727 is administered on days 1–5 of each cycle and ven on days 1–28 of the 1st cycle (21 days in subsequent cycles). Ven is held if blast <5% on day 21±3 bone marrow. Results: Between March 2021 and January 2022, 28 pts (15 FL,13 R/R) were treated. The median age is 75 years (range, 47–90); 81 in the FL cohort and 72 in the R/R cohort. Nine FL pts (60%) were ≥80 and 5 (30%) were 70–80 years. In the R/R cohort, 9 pts (69%) were 70–80 years. The median PS is 2. The R/R cohort had a median of 2 prior treatments (range, 1–4). In the FL cohort, 5 (33%) had normal and 6 (40%) a complex karyotype; 3 had other. In the R/R cohort, 15% had normal and 46% a complex karyotype and 31% had other. Mutations in the FL cohort were RUNX1 (33%), ASXL1 (33%), DNMT3A (7%), TET2 (40%), and TP53 (20%). Overall response in the FL cohort is 61% (4 complete response [CR], 4 CR with incomplete count recovery [Cri], 1 morphological leukemia-free state [MLFS], 3 non-responders) and 45% in the R/R cohort (2 CR, 2 CRi, 2 MLFS, 5 non-responders, 2 not-evaluable). Both cohorts received a median of 2 cycles (range, 1–5). With a median follow-up of 5 months, the median survival for the FL cohort has not been reached (range, 0.6–7.3) and is 7.2 (range, 0.8–7.3) months for the R/R cohort. Grade ≥3 adverse events were neutropenic infections in 3 (11%) and liver enzymes elevation in 1 (4%). Conclusions: ASTX727 and venetoclax combination is safe and feasible and demonstrates significant efficacy in pts unfit for chemotherapy. Research funding by Taiho.

Original languageEnglish
Pages (from-to)S237
JournalClinical Lymphoma, Myeloma and Leukemia
Volume22
DOIs
StatePublished - Oct 2022
Externally publishedYes

Keywords

  • AML
  • ASTX27
  • Phase II
  • decitabine
  • unfit

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