guadecitabine (SGI-110) / Otsuka - LARVOL DELTA

Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer (clinicaltrials.gov) - P1 | N=55 | Active, not recruiting | Sponsor: University of Southern California | Trial completion date: Dec 2025 ➔ Jul 2026

Trial completion date • Biliary Cancer • Cholangiocarcinoma • Gallbladder Cancer • Hepatocellular Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Location and deprivation in silicosis cases: data from the SWORD scheme 1996–2024 (BTS WM 2025) - "Download figure Open in new tab Download powerpoint Abstract S110 Figure 1 Conclusion Despite being preventable silicosis continues to occur in the UK. Most cases were from low/middle IMD deciles and from regions with higher levels of deprivation suggesting silicosis disproportionately affects people with higher deprivation in the UK. More research should focus on the complex factors increasing the risk of disease, and on improved disease prevention, for these groups."

Clinical • Pulmonary Disease • Respiratory Diseases

Analysis of ASXL1 Mutated T Cells in Patients with Myeloid Malignancies (ASH 2023) - "in 2022, patients with MDS and CMML previously exposed to HMA were treated with a combination of atezolizumab, an immune checkpoint inhibitor (ICI), and guadecitabine, an HMA. We obtained peripheral blood samples from eight patients with ASXL1 mutated myeloid neoplasms detected by commercial NGS testing; aspirate was also obtained from a diagnostic BM biopsy in one patient. Table 1 shows patient demographics, characteristics and mutational analyses in both T and myeloid cells. Most patients were treatment-naïve, but one had been treated with HMA until 6 months prior to sample collection, and one patient had received cyclosporine for over 20 years for an undiagnosed autoimmune condition."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • ASXL1 • CD34 • CD8

Long-Term Follow-up and T Cell Characteristics of Patients with ASXL1-Mutated Relapsed or Refractory MDS or CMML Treated with Guadecitabine and Atezolizumab (ASH 2023) - "Herein we report long-term follow-up of this cohort of patients, along with T cell programmed death-1 (PD-1) expression analyzed based on mutational status. Significant upregulation of PD-1 was noted in T lymphocytes from both wild-type and co-mutated patients. The effect of mutant ASXL1 on T cell responsiveness to ICI deserves further investigation; patients with ASXL1-mutated HMA-refractory myeloid malignancies may benefit from ICI."

Clinical • IO biomarker • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ASXL1 • CD8 • PD-1 • TP53

Update of a Phase II Trial of Guadecitabine in Higher-Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia Under the International Working Group 2023 Criteria (ASH 2023) - "From 2014 to 2018, 82 patients with MDS and 18 patients with CMML were enrolled and treated. Median age was 69 (IQR 62.5 – 75), 62% were male, 38.4% had complex karyotype, 86.6% were categorized as IPSS-M high or very-high risk. Additionally, 33.7% were TP53mut, 21.4% were TP53multi-hit."

P2 data • Chronic Myelomonocytic Leukemia • Constipation • Fatigue • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • ASXL1 • DNMT3A • NRAS • SRSF2 • TET2 • TP53

Anti-CD40 and Epigenetic Modifier Inhibitors to Augment Treatment of High-Risk Neuroblastoma (SITC 2025) - "We identified inhibitors of DNMTs (guadecitabine, 'Guad') and HDACs (entinostat, 'Ent') that, when combined with aGD2 and aCD40, cause tumor regression.Methods HR-NBL cells were treated with EMis and assessed for MHCI expression changes via qPCR and flow cytometry. Therapies geared towards restoring MHCI expression, combined with effective immunotherapy regimens that allow for persistent immune responses, might augment immune responses and improve efficacy of combination immunotherapy for HR-NBL.Ethics Approval Our research is conducted under strict oversight by the IACUC and in compliance with all applicable federal and institutional policies.Acknowledgements This research was supported by Midwest Athletes Against Childhood Cancer; and by public health service grants from the National Cancer Institute: Alex's Lemonade Stand Foundation, the Hartwell Foundation, Midwest Athletes Against Childhood Cancer, R35 CA197078, U54 CA232568 as well as the Data..."

IO biomarker • Neuroblastoma • Oncology • Solid Tumor

ETCTN: Testing the Combination of Belinostat and SGI-110 (Guadecitabine) or ASTX727 for the Treatment of Unresectable and Metastatic Conventional Chondrosarcoma (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Oncology • Sarcoma • Solid Tumor

Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies. (PubMed, Pharmaceuticals (Basel)) - "DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling...Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases."

IO biomarker • Journal • Review • Gene Therapies • Lung Cancer • Oncology • Solid Tumor • KLF5 • MIR34A • NORAD • RASSF1 • SMARCA4

S-110: Chrononutrition to optimize health (WSS 2025) - No abstract available

Pembrolizumab (Immunotherapy Drug) in Combination With Guadecitabine and Mocetinostat (Epigenetic Drugs) for Patients With Advanced Lung Cancer. (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2025 ➔ Jul 2026 | Trial primary completion date: Jul 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

NCI-2016-01233: Guadecitabine and Atezolizumab in Treating Patients With Advanced Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia That Is Refractory or Relapsed (clinicaltrials.gov) - P1/2 | N=33 | Active, not recruiting | Sponsor: University of Southern California | Trial completion date: Nov 2025 ➔ Dec 2026 | Trial primary completion date: Nov 2024 ➔ Dec 2025

Checkpoint inhibition • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Guadecitabine improved relapse-free survival in high-risk acute myeloid leukemia and myelodysplastic syndrome patients after transplant: phase II results from a single center. (PubMed, Haematologica) - "No unexpected adverse events (AEs) occurred, and no graft failures were observed. Guadecitabine demonstrated efficacy and a favorable safety profile across all cohorts, supporting the investigations of hypomethylating agents."

Journal • P2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Leber's hereditary optic neuropathy-associated ND1 3733G> C mutation ameliorates the mitochondrial quality control and cellular homeostasis. (PubMed, J Biol Chem) - "Molecular dynamics simulations showed that p.E143Q mutation destabilized these interactions between residues E143 and S110/Y114, or between S141 and W290 in the ND1...The m.3733G>C mutation-induced deficiencies reshaped the cellular homeostasis via impairing autophagy process and promoting intrinsic apoptosis. Our findings provide new insights into pathophysiology of LHON arising from the m.3733G>C mutation-induced mitochondrial dysfunctions and reprograming organellular and cellular homeostasis."

Journal • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • Retinal Disorders • Targeted Protein Degradation

s110: Indolent lymphoma (EHA 2025) - No abstract available

Hematological Malignancies • Indolent Lymphoma • Lymphoma • Oncology

The phase II NIBIT-ML1 study of nivolumab plus ipilimumab and ASTX727 or nivolumab plus ipilimumab in PD-1 resistant metastatic melanoma: Tumor methylation landscape and correlation with clinical outcomes. (ASCO 2025) - P2 | "Funded by No funding sources reported Clinical Trial Registration Number: NCT04250246 Background: In the NIBIT Foundation-sponsored phase Ib NIBIT-M4 study, we firstly showed that the hypomethylating agent (HMA) guadecitabine (guade), a prodrug of decitabine (D), followed by ipilimumab (I) was safe with promising clinical and immunologic activity in cutaneous metastatic melanoma (MM) patients (pts) (Di Giacomo, Clin Cancer Res 2019; Noviello, Nat Commun 2023). Treatment with ASTX727 plus I+N is feasible and has meaningful clinical and immunologic activity in PD-1 refractory MM pts."

Clinical • Clinical data • Late-breaking abstract • Metastases • P2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-1

ETCTN: Testing the Combination of Belinostat and SGI-110 (Guadecitabine) or ASTX727 for the Treatment of Unresectable and Metastatic Conventional Chondrosarcoma (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2026 ➔ Jun 2025

Trial completion date • Oncology • Sarcoma • Solid Tumor

ETCTN: Testing the Combination of Belinostat and SGI-110 (Guadecitabine) or ASTX727 for the Treatment of Unresectable and Metastatic Conventional Chondrosarcoma (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=32 ➔ 20 | Trial completion date: Jun 2025 ➔ May 2026

Enrollment change • Trial completion date • Oncology • Sarcoma • Solid Tumor

Blood based biomarkers of DNA methylation associated with platinum resistance in high grade serous ovarian cancer (AACR 2025) - P2 | "The Pt-resistant patients were enrolled on NCT02901899 clinical trial testing guadecitabine and pembrolizumab. We propose new DMLs associated with Pt-sensitive vs. Pt-resistant OC. These findings can lead to new biomarkers for HGSOC."

Biomarker • Epigenetic controller • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD4 • CD8

DNA methylation profiling of peripheral blood mononuclear cells from small-cell lung cancer patients treated with hypomethylating agent plus carboplatin (AACR 2025) - "Small-cell lung cancer (SCLC), representing 15% of lung cancers, is one of the deadliest malignancies, with a 5-year survival rate under 7%. These findings demonstrate that guadecitabine treatment induces significant CpG methylation changes in PBMCs, impacting genes and pathways critical to cellular signaling, tissue remodeling, and survival mechanisms. The identification of key pathways, including those involved in metastasis, lung remodeling, and tumor cell survival, highlights the potential role of HMAs in modulating epigenetic and biological processes relevant to SCLC progression and therapy."

Clinical • Epigenetic controller • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD4 • CD8 • NGFR

DNA methylation status classifies pleural mesothelioma cells according to their immune profile: implication for precision epigenetic therapy (AACR 2025) - "Therefore, we utilized a panel of cultured PM cells of different histotype to provide preclinical evidence supporting the role of the tumor methylation landscape and of its pharmacologic modulation, to prospectively improve the efficacy of ICI therapy of PM patients. the methylome profile (EPIC array) of distinct E (n=5) and non-E (n=9) PM cell lines was analyzed, followed by integrated analysis with their associated transcriptomic profile (Clariom S array), before and after in vitro treatment with the DNA hypomethylating agent (DHA) guadecitabine... the study highlighted the relevance of DNA methylation in shaping the constitutive immune classification of PM cells, independent of their histological subtypes. The identified role of DHA in shifting the phenotype of PM cells towards an immune-favorable state supports its potential role in clinical trials of precision epigenetic therapy combined with ICI."

Epigenetic controller • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor

Treatment landscape in SDH-deficient gastrointestinal stromal tumors: A systematic review and meta-analysis (Sarcoma-RC 2025) - "Treatments examined included Imatinib, Sunitinib, Regorafenib, Pazopanib, Masitinib, Vandetanib, Guadecitabine, and Linsitinib. Legal entity responsible for the study The authors. Funding Has not received any funding."

Retrospective data • Review • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | N=75 ➔ 12

Enrollment change • IO biomarker • Trial completion • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B • PD-L1

Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer (clinicaltrials.gov) - P1 | N=55 | Active, not recruiting | Sponsor: University of Southern California | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Mar 2021 ➔ Apr 2024

Trial completion date • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Gallbladder Cancer • Hepatocellular Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment. (PubMed, Curr Oncol) - "Improving the treatment schedules, increasing isoform specificity, reducing toxicity, and utilizing genome-wide analyses of CRISPR-based editing to create personalized epigenetic therapies tailored to individual patient needs are promising strategies for enhancing therapeutic outcomes. This review discusses the interaction between DNMT regulators and DNMT1, its binding partners, the connection between DNA methylation and tumors, how these processes contribute to tumor development, and DNMT inhibitors' advancements and pharmacological properties."

IO biomarker • Journal • Review • Gene Therapies • Oncology • DNMT1

DNA methylation status classifies pleural mesothelioma cells according to their immune profile: implication for precision epigenetic therapy. (PubMed, J Exp Clin Cancer Res) - "The study highlighted the relevance of DNA methylation in shaping the constitutive immune classification of PM cells, independent of their histological subtypes. The identified role of DHA in shifting the phenotype of PM cells towards an immune-favorable state highlights its potential for evaluation in phase I/II clinical trials investigating the efficacy of epigenetic-based ICI combinations to reverse cancer immune resistance mechanisms."

Journal • Gene Therapies • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor