Onureg (azacitidine oral) / BMS - LARVOL DELTA

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

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 | Suspended | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Suspended

Trial suspension • Hepatology • Myelodysplastic Syndrome • Oncology

Testing CC-486 (Oral Azacitidine) Plus the Standard Drug Therapy in Patients 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma (clinicaltrials.gov) - P2/3 | N=422 | Suspended | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • B Cell Lymphoma • Breast Cancer • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Hodgkin Lymphoma • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Nodular Lymphocyte Predominant Hodgkin Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type • T Cell Histiocyte Rich Large B Cell Lymphoma • Waldenstrom Macroglobulinemia • BCL2 • BCL6 • CD4

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

MIVONU: Study Evaluating the Efficacy and Safety of the Addition of Ivosidenib to Oral Azacitidine (Onureg®) in Patients Over 55 With Acute Myeloid Leukemia (AML) and IDH1 Mutation, in Complete Remission After Intensive Chemotherapy. (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: French Innovative Leukemia Organisation

New P2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1

Effectiveness and Safety of ONUREG (Oral Azacitidine) in Chinese Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - P=N/A | N=44 | Active, not recruiting | Sponsor: Bristol-Myers Squibb

New trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

FILO-AML-01-MIVONUnA single arm phase II study investigating the efficacy and safety of the addition of ivosidenib to oral azacitidine (Onureg) in patients over 55 with Acute Myeloid Leukemia (AML) and IDH1 mutation, in complete remission after intensive chemotherapy. A study of the French AML Intergroup. (clinicaltrialsregister.eu) - P1/2 | N=60 | Not yet recruiting | Sponsor: French Innovative Leukemia Organization

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1

Fedratinib in combination with CC-486, an oral hypomethylating agent, in Patients with accelerated Phase myelofibrosis: Results from the phase I/II multicenter FAMy trial (DRKS00030348) (DKK 2026) - "For the first time, the feasibility of combining 300mg FED with CC-486 in MPN-AP is shown. Considering the dismal prognosis and lack of optimal therapies for MPN-AP, the encouraging results of this trial warrant further evaluation."

Clinical • Combination therapy • P1/2 data • Hematological Disorders • Infectious Disease • Myelofibrosis

ASTREON: A Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Participants With International Prognostic Scoring System Revised (IPSS-R) Low- or Intermediate-risk Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P2/3 | N=230 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jul 2026 ➔ Jul 2028 | Trial primary completion date: Jan 2026 ➔ Jul 2028

Trial completion date • Trial primary completion date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Study of Oral Azacitidine (CC-486) in Combination With Pembrolizumab (MK-3475) in Patients With Metastatic Melanoma (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Feb 2026 ➔ Dec 2026 | Trial primary completion date: Feb 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Melanoma • Oncology • Skin Cancer • Solid Tumor

RELION: Characteristics and Outcomes of Acute Myeloid Leukemia (AML) Patients Treated With Oral-Azacitidine Maintenance Therapy in France (clinicaltrials.gov) - P=N/A | N=112 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Jan 2026 | Trial primary completion date: Oct 2024 ➔ Jan 2026

Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

T-LGLL: Oral Azacitidine for the Treatment of Relapsed or Refractory T-cell Large Granular Lymphocytic Leukemia (clinicaltrials.gov) - P1/2 | N=11 | Active, not recruiting | Sponsor: Jonathan Brammer | Trial completion date: Jan 2026 ➔ Jun 2026 | Trial primary completion date: Jan 2026 ➔ Jun 2026

IO biomarker • Trial completion date • Trial primary completion date • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • T-Cell Large Granular Lymphocyte Leukemia • CD4 • CD8 • IL15

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

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