Onureg (azacitidine oral) / BMS - LARVOL DELTA

Pembrolizumab and epigenetic modification with azacitidine reshapes the tumor microenvironment of platinum-resistant epithelial ovarian cancer: a phase 2 non-randomized clinical trial. (PubMed, Commun Med (Lond)) - P2 | "Our findings highlight the potential of epigenetic modulators to re-shape the tumor microenvironment of PROC toward a more inflammed phenotype and may point to approaches to augment immunotherapy response."

Biomarker • Clinical • IO biomarker • Journal • P2 data • Platinum resistant • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Hematological Disorders • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CD8 • MUC16

Targeting the methylome in T-LGL leukemia: Pre-clinical analysis and Results of a Phase I trial with oral 5-azacytidine (ASH 2025) - P1/2 | "In vivo, NSG huIL-15 mice engrafted with LGLLcells and treated with 5-aza (3 mg/kg) showed significant LGLL reduction via IVIS imaging and improvedoverall survival (n=5 each, p<0.001), supporting the potential of epigenetic therapy in LGLL therapy.Given the strong preclinical impact of 5-aza on T-LGLL cells, we initiated a multi-center Phase I/II trialusing oral 5-aza (CC-486) in relapsed/refractory T-LGLL patients (NCT05141682)...In vitro, in vivo, and Phase I trial datashow that epigenomic targeting with 5-aza yields clinical responses across doses without DLTs. The PhaseII component of the oral 5-aza clinical trial is currently ongoing, reinforcing the critical role of themethylome in T-LGLL pathogenesis."

P1 data • Preclinical • Gene Therapies • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • T-Cell Large Granular Lymphocyte Leukemia • CD5 • CD8 • IL15

USE OF ORAL AZACITIDINE AS BRIDGING THERAPY TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLO-HSCT): A SINGLE TRANSPLANT PROGRAM EXPERIENCE (EBMT 2026) - "Oral azacitidine as bridging therapy to allo-HSCT in patients with intermediate/high-risk AML is feasible and seems effective in maintaining hematological and molecular CR, including FLT3 mutated cases. Futhermore, in our cohort, no patients did not undergo allo-HSCT due to azacitidine related adverse events. Although our experience is limited to a small series, these data are encouraging for the use of oral azacitidine as bridging therapy in case of allo-HSCT delay."

Bone Marrow Transplantation • Transplantation • FLT3

High Rates of Remission with the Initial Treatment of Oral Azacitidine Plus CHOP for Peripheral T-Cell Lymphoma (PTCL): Clinical Outcomes and Biomarker Analysis of a Multi-Center Phase II Study (ASH 2021) - P2 | "This study demonstrates that priming with oral azacitidine (CC486) in combination with CHOP as initial therapy is safe, effective, and produces sustained remission in PTCL-TFH subtype. Epigenetic priming with azacitidine appears to inhibit the proliferation of TFH lymphoma cells, providing potential synergistic mechanism of action with chemotherapy. This active combination will be further evaluated in the upcoming ALLIANCE/ US Intergroup randomized study A051902, comparing oral azacitidine-CHO(E)P vs duvelisib-CHO(E)P against CHO(E)P in CD30 negative PTCL."

Biomarker • Clinical • Clinical data • P2 data • Anemia • Anorexia • Bone Marrow Transplantation • Cardiovascular • Fatigue • Febrile Neutropenia • Heart Failure • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • Transplantation • DNMT3A • IDH2 • RHOA • TET2 • TNFRSF8 • TRB

Results from a Phase 1 Open-Label Dose Escalation and Expansion Trial of Oral Azacitidine + Cedazuridine (ASTX030) in Patients with Myelodysplastic Syndromes (MDS) and MDS/Myeloproliferative Neoplasms (MPN) (ASH 2024) - P2/3 | "Background : Azacitidine (AZA) and decitabine (DEC) are parenteral DNA methyltransferase inhibitors (DNMTis) approved for the treatment of patients with MDS and acute myeloid leukemia...Median age was 72 years (range, 26–87), 35% (n=31) of patients were female, prior treatments included DNMTis (9% [n=8]), luspatercept (3% [n=3]), lenalidomide (3% [n=3]), and erythropoiesis‑stimulating agents (3% [n=2])...Based on the results of the phase 1 trial, 140/20 mg AZA/CED was selected as the RP2D. Enrollment for the phase 2 randomized, crossover (oral vs SC) trial is ongoing and combination dosing is in preparation."

Clinical • P1 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytopenia

Preliminary safety and efficacy of oral azacitidine (Oral-AZA) in patients (pts) with low-/Intermediate (Int)-risk myelodysplastic syndromes (MDS): Phase 2 results from the ASTREON trial. (ASCO 2024) - P2/3 | "Most pts (42/47 [89.4%]) had prior MDS tx, including but not limited to erythropoiesis-stimulating agents, lenalidomide, luspatercept, and imetelstat. The safety of Oral-AZA 200 mg and 300 mg was consistent with the known Oral-AZA safety profile. Preliminary efficacy data support continued evaluation of Oral-AZA in LR-MDS."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Romidepsin, CC-486 (5-azacitidine), Dexamethasone, and Lenalidomide (RAdR) for Relapsed/Refractory T-cell Malignancies (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: May 2026 ➔ Dec 2025

Trial completion • Trial completion date • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

CLINICAL AND BIOLOGICAL MARKERS ASSOCIATED WITH LONG-TERM SURVIVAL FOR PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) IN REMISSION AFTER CHEMOTHERAPY IN THE QUAZAR AML-001 TRIAL OF ORAL AZACITIDINE (EHA 2022) - "Conclusion Oral-AZA Tx was significantly associated with LTS vs PBO. In univariate analysis, Int-risk cytogenetics and NPM1 mut at Dx, and MRD response on-study, were significantly prognostic of LTS in both arms, whereas MRD– status at BL (post-IC) was associated with LTS only in the PBO arm."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD4 • CD8 • FLT3 • HAVCR2 • NPM1 • PD-1

Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study. (PubMed, Lancet Haematol) - P3 | "Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial."

Clinical • IO biomarker • Journal • P3 data • P3 data • Candidiasis • Cardiovascular • Congestive Heart Failure • Follicular Lymphoma • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • T Cell Non-Hodgkin Lymphoma • BCL6 • CXCL13 • ICOS • MME • PD-1

Multicenter Phase 2 Study of Oral azacitidine (CC-486) plus CHOP as initial treatment for peripheral T-cell lymphoma. (PubMed, Blood) - P2 | "DNA methylation did not show significant shift. This safe and active initial therapy regimen is being further evaluated in the ALLIANCE randomized study A051902 in CD30-negative PTCL."

Journal • P2 data • Fatigue • Febrile Neutropenia • Hematological Malignancies • Immunology • Lymphoma • Neutropenia • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • DNMT3A • IDH2 • RHOA • TET2 • TNFRSF8

ORAL AZACITIDINE VS MIDOSTAURIN AS MAINTENANCE TREATMENT FOR FLT3 MUTANT ACUTE MYELOID LEUKEMIA IN COMPLETE REMISSION: AN INDIRECT TREATMENT COMPARISON (EHA 2022) - P3 | "Limitations included trial differences and small sample size. More research is needed to support this observation."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • FLT3

A Phase II Study of Azacitidine Plus Venetoclax As Maintenance Therapy in Acute Myeloid Leukemia: Durable Responses with Longer Term Follow-up (ASH 2022) - P2 | "Oral azacitidine (CC-486) has been shown to improve relapse-free survival (RFS) and overall survival (OS) in patients with AML who have achieved first complete remission (CR) after intensive chemotherapy, and is currently the only agent approved as maintenance therapy in AML... This phase II study enrolled patients with AML ≥ 18 years, not immediately eligible for SCT, and who had achieved a first CR/CRi (regardless of measurable residual disease [MRD] status) following at least 2 cycles of intensive chemotherapy (defined as intermediate or higher dose cytarabine; cohort 1) or low-intensity therapy (defined as hypomethylating agent or low-dose cytarabine-based; cohort 2)... With over 13 months of follow up, this is the first experience demonstrating the tolerability and feasibility of low-dose AZA plus VEN as maintenance therapy in AML. RFS and OS are encouraging, especially in the non-adverse risk ELN categories (favorable or intermediate). Further studies are..."

Clinical • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Thrombocytopenia • Transplantation

Reduced dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia following intensive or low-intensity induction: a single-centre, single-arm, phase 2 trial. (PubMed, Lancet Haematol) - P2 | "Low dose azacitidine plus venetoclax is a feasible maintenance strategy in acute myeloid leukaemia following intensive and low-intensity induction."

Journal • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Neutropenia • Oncology • Respiratory Diseases • Thrombocytopenia • Transplantation

Oral azacitidine prolongs survival of patients with AML in remission independent of measurable residual disease status. (PubMed, Blood) - P3 | "While presence or absence of MRD was a strong prognostic indicator of OS and RFS, there were added survival benefits with Oral-AZA maintenance therapy compared with placebo, independent of patients' MRD status at baseline. NCT01757535 Clinicaltrials.gov."

Clinical • Journal • Residual disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Results from a Clinical Study of the All-Oral Regimen of CC-486 (Oral Azacitidine) and Venetoclax for Newly Diagnosed and Relapsed and Refractory Acute Myeloid Leukemia (ASH 2024) - "The MTD of CC-486 in combination with ven was previously reported as 300mg QD d1-14 in relapsed/refractory (R/R) AML (Amaya et al. High response rates have been seen in the newly diagnosed cohort with 7/7 (100%) of the patients achieving a CR/CRi, including 3/3 who harbor a TP53 mutation. Final results of the R/R cohort, as well as a larger sample size of the ND subjects, with genomic annotation, as well as translational studies exploring mechanistic differences and similarities with this all-oral regimen and conventional aza/ven, will be presented."

Clinical • Acute Myelogenous Leukemia • Anemia • Fatigue • Febrile Neutropenia • Neutropenia • Thrombocytopenia • TP53

CLONAL ARCHITECTURE OF RELAPSED OR REFRACTORY FOLLICULAR HELPER T-CELL LYMPHOMA: AN ANCILLARY STUDY OF THE ORACLE TRIAL, A LYSA STUDY (ICML 2023) - P3 | "To describe and characterize the clonal architecture of refractory/relapsed (R/R) TFHL, we collected bone marrow samples of patients included in the ORACLE trial (NCT03593018), a phase 3 trial evaluating the oral 5-azacitidine (CC-486) compared to single-agent chemotherapy in patients with R/R TFHL...In conclusion, CH is very frequent in TFHL, and more than half of them are TFHL-related. Encore Abstract—previously submitted to EHA 2023"

Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • DNMT3A • IDH2 • RHOA • TET2

Prognostic impact of NPM1 and FLT3 mutations in patients with AML in first remission treated with oral azacitidine. (PubMed, Blood) - P3 | "Median OS with Oral-AZA vs placebo was 28.2 vs 16.2 months, respectively, for FLT3mut/MRD- patients, and 24.0 vs 8.0 months for FLT3mut/MRD+ patients. In multivariate analyses, Oral-AZA significantly improved survival independent of NPM1 or FLT3 mutational status, cytogenetic risk, or post-IC MRD status."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Transplantation • FLT3 • NPM1

A POST HOC ANALYSIS OF OUTCOMES OF PATIENTS WITH ACUTE MYELOID LEUKEMIA WITH MYELODYSPLASIA-RELATED CHANGES WHO RECEIVED ORAL AZACITIDINE MAINTENANCE THERAPY IN THE QUAZAR AML-001 STUDY (EHA 2024) - "Oral-AZA significantly improved OS and RFS compared with PBO for patients with AML-MRC indicating that Oral-AZA maintenance is an effective treatment option for these patients with particularly poor prognosis."

Clinical • Retrospective data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Oral Azacytidine in Patients with Relapsed/Refractory Angioimmunoblastic T-Cell Lymphoma: Final Analysis of the Oracle Phase III Study (ASH 2022) - P3 | "Patients & Eighty-six patients with relapsed/refractory AITL or nodal follicular helper T-cell lymphoma were randomized between CC-486 (n=42) and investigator's choice (gemcitabine, n=24, bendamustine n=16, romidepsin n=4) between November 2018 and February 2021. The trial did not meet its primary endpoint, most likely due to an optimistic hypothesis of PFS improvement, resulting in a study including 86 patients which could be underpowered to detect a clinically meaningful difference. 5-azacytidine had a favourable safety profile compared to standard of care and was associated with prolonged overall survival, suggesting that this drug might have a role in the treatment of TFH PTCL and could be investigated in combination with other agents."

Clinical • P3 data • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • DNMT3A • IDH2 • RHOA • TET2

Long-term survival with oral azacitidine for patients with acute myeloid leukemia in first remission after chemotherapy: updated results from the randomized, placebo-controlled, phase 3 QUAZAR AML-001 trial. (PubMed, Am J Hematol) - No abstract available

Journal • P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

FDA Approval Summary: Oral Azacitidine For Continued Treatment of Adults with Acute Myeloid Leukemia Unable to Complete Intensive Curative Therapy. (PubMed, Clin Cancer Res) - "Additional studies are needed to establish safe dosing for patients with hepatic impairment. The pharmacokinetic parameters, recommended dose, and recommended schedule of CC-486 differ substantially from those of other azacitidine formulations; therefore, inappropriate substitutions between formulations pose a considerable risk for harm."

FDA event • Journal • Acute Myelogenous Leukemia • Fatigue • Gastrointestinal Disorder • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases

A Study to Evaluate CC-486/Onureg in Participants With Moderate or Severe Hepatic Impairment Compared With Normal Hepatic Function in Participants With Myeloid Malignancies (clinicaltrials.gov) - P1 | N=2 | Terminated | Sponsor: Bristol-Myers Squibb | N=32 ➔ 2 | Active, not recruiting ➔ Terminated; Insufficient Enrollment

Enrollment change • Trial termination • Hepatitis C • Hepatology • Liver Failure • Myelodysplastic Syndrome • Oncology

Trial in progress: A Phase IIb randomized clinical trial combining oral azacitidine and vididencel, a novel immunotherapy, for post-remission / maintenance therapy for adult patients with cytogenetically intermediate and high-risk Acute Myeloid Leukemia (ALLG AMLM22/D4 CADENCE) (ASH 2025) - "We gratefully acknowledge the patients and families. Contact: www.allg.org.au"

Clinical • IO biomarker • P2b data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma

Oral azacitidine maintenance therapy for patients with acute myeloid leukaemia and myelodysplasia-related changes: Post hoc analysis of the QUAZAR AML-001 trial. (PubMed, Br J Haematol) - No abstract available

Journal • Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Trials in progress: Phase IB/II of CPX-351 as maintenance therapy in AML patients ineligible for bone marrow transplantation (ASH 2025) - "In patients ineligible for allogenic hematopoietic stem cell transplant (HSCT), oral azacitidine is the only FDA approved treatment option...Eligible patients are newly diagnosed with AML in CR that have received any induction regimen with standard consolidation or a hypomethylating agent (HMA) and venetoclax, for at least 6 cycles and no more than 12 cycles...Prior HSCT patients are excluded, as well as cumulative lifetime anthracycline (doxorubicin equivalent) dose equal to or greater than 345 mg/m2, and for patients with prior mediastinal radiation therapy, anthracycline dose equal to or greater than 295 mg/m2...This investigator-sponsored study was supported by a research grant and provision of study drug from Jazz Pharmaceuticals. The study was independently designed and conducted by the investigators."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Transplantation