P1/2, N=32, Recruiting, Australasian Leukaemia and Lymphoma Group | Not yet recruiting --> Recruiting

P1, N=18, Recruiting, Astex Pharmaceuticals, Inc. | Phase classification: P1b --> P1

P1, N=27, Recruiting, Astex Pharmaceuticals, Inc. | Phase classification: P1b --> P1

P1, N=18, Recruiting, Pamela Munster | Not yet recruiting --> Recruiting

P1, N=30, Active, not recruiting, Otsuka Pharmaceutical Co., Ltd. | Trial completion date: Dec 2023 --> Jan 2026 | Trial primary completion date: Dec 2023 --> Jan 2026

P1, N=15, Not yet recruiting, Case Comprehensive Cancer Center

P1/2, N=188, Active, not recruiting, Astex Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting

P1/2, N=132, Active, not recruiting, Astex Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting

P1, N=18, Recruiting, Massachusetts General Hospital | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2022 --> May 2024

P2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P1, N=34, Completed, Kathy Miller | Recruiting --> Completed | Trial completion date: Jul 2025 --> Mar 2024 | Trial primary completion date: Dec 2024 --> Jan 2024

P1, N=34, Recruiting, Royal Marsden NHS Foundation Trust | Active, not recruiting --> Recruiting

P1, N=12, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Oct 2024 --> Jun 2025 | Trial primary completion date: Apr 2024 --> Dec 2024

P3, N=42, Recruiting, Otsuka Australia Pharmaceutical Pty Ltd | Not yet recruiting --> Recruiting | Phase classification: P3b --> P3

P1, N=58, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P2, N=20, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

ASTX727 plus venetoclax is an active fully oral regimen and safe in most older or unfit patients with acute myeloid leukaemia. Our findings should be confirmed in larger multicentric studies.

P2, N=65, Not yet recruiting, M.D. Anderson Cancer Center

P1, N=48, Not yet recruiting, Novo Nordisk A/S

P1/2, N=36, Not yet recruiting, M.D. Anderson Cancer Center

P1/2, N=13, Active, not recruiting, Massachusetts General Hospital | Trial primary completion date: Dec 2023 --> Jan 2025

P1/2, N=42, Suspended, M.D. Anderson Cancer Center | Phase classification: P1b/2a --> P1/2 | Not yet recruiting --> Suspended

P1/2, N=42, Suspended, M.D. Anderson Cancer Center

P2, N=51, Recruiting, Sanjay Mohan | Trial completion date: Dec 2028 --> Mar 2029 | Initiation date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2027 --> Mar 2028

P2, N=15, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P1, N=29, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024

P1, N=58, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=32, Suspended, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P2, N=51, Recruiting, Sanjay Mohan

P1/2, N=55, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P1, N=18, Not yet recruiting, Pamela Munster

P1, N=38, Recruiting, Kathy Miller | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=84, Recruiting, Novo Nordisk A/S | Trial primary completion date: Nov 2023 --> Oct 2024

P1, N=24, Recruiting, National Cancer Institute (NCI) | Initiation date: Feb 2024 --> Sep 2023

Descriptive statistics including frequencies, proportions, mean, standard deviation, median, and interquartile range will be used to summarize the study data. When complete, this study will address an evidence gap in the comparison of patient preference for oral decitabine/cedazuridine and SC AZA, and subsequently inform the value of oral decitabine/cedazuridine for the treatment of MDS, LB-AML and CMML.

P1, N=24, Recruiting, National Cancer Institute (NCI) | Initiation date: Nov 2023 --> Feb 2024

P1/2, N=80, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P1, N=27, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

Azacitidine (AZA) and decitabine (DEC; including oral cedazuridine/decitabine) are the only FDA-approved HMAs. Among pts included in the real-world VALIDATE database, there were no significant difference in OS or ORR (IWG 2023) between AZA- and DEC-treated pts in adjusted analyses. Other factors (e.g., TP53 mutations, complex karyotype) are substantially more relevant to outcomes than the specific HMA used. The small number of pts and heterogeneity of partner drugs in HMA-based combinations precluded robust analyses or conclusions regarding differences in efficacy.

Background: Hypomethylating agents (HMA), such as decitabine, azacitidine, and oral decitabine/cedazuridine, are standard-of-care therapies for patients with myelodysplastic syndromes (MDS)... In this group of MDS patients treated with HMA, patients who eventually developed HMA-F were older with higher BM blasts and higher-risk disease by IPSS-R and IPSS-M. No statistically significant differences were observed by HMA therapy details, cytogenetics, and specific mutations, but those with multiple mutations in the same gene tended to remain on HMA therapy. Further investigation into predictors of HMA-F and potential other treatment modalities is warranted.

An oral regimen of 10-day ASTX727 with venetoclax showed safety profile comparable to other venetoclax-based regimens in R/R AML and responses occurred in ELN adverse risk venetoclax-naïve pts. Novel therapies are needed for patients progressing on prior BCL2 inhibitor-based regimens.

In this older and very high-risk population of pts with AML, an entirely oral regimen consisting of ASTX727 and venetoclax was effective and tolerable.