guadecitabine (SGI-110) / Otsuka - LARVOL DELTA

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

Hypomethylating agents as emerging therapeutics for triple-negative breast cancer. (PubMed, Life Sci) - "Hypomethylating agents (HMAs) such as azacitidine, decitabine, and guadecitabine are key inhibitors of DNMTs, and accumulating evidence has shown their immunogenicity properties. More clinical studies are required to establish the effectiveness of HMAs against the disease, as supported by preclinical data substantiating their effectiveness especially guadecitabine. Future research should focus on optimizing dosing and exploring combinations with immunotherapies to maximize the potential of HMAs in TNBC treatment."

IO biomarker • Journal • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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=32 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jan 2025 ➔ Jun 2025 | Trial primary completion date: Jan 2025 ➔ Jun 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Solid Tumor • IDH1 • IDH2

[PREPRINT] Bone marrow microenvironment signatures associate with patient survival after guadecitabine and atezolizumab therapy in HMA-resistant MDS (bioRxiv) - P1/2 | N=33 | NCT02935361 | "This combination therapy showed median overall survival of 15.1 months relative to historical controls (4-6 months). Here, we profiled the cell composition and gene expression signatures of cells from bone marrow aspirates from trial participants with short-term (15 months) survival at single-cell resolution. Long-term survivors showed a significant reduction of immunosuppressive monocytes, and an expansion of effector lymphocytes after combination therapy. Further immune profiling suggests that gamma delta T cell activation through primed dendritic cells was associated with global interferon activation in the bone marrow microenvironment of long-term survivors."

P1/2 data • Preprint • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Bone marrow microenvironment signatures associate with patient survival after guadecitabine and atezolizumab therapy in HMA-resistant MDS. (PubMed, bioRxiv) - "Short-term survivors exhibited elevated inflammation and senescence-like gene signatures that were not resolved by combination therapy. We propose that distinct bone marrow microenvironment features, such as senescence-associated inflammation or immunosuppressive monocyte presence, could improve patient stratification for HMA and immunotherapy combinations in HMA-R/R MDS patients."

IO biomarker • Journal • Hematological Malignancies • Inflammation • Myelodysplastic Syndrome • Oncology

NCI-2016-00343: Guadecitabine and Donor Lymphocyte Infusion in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Relapsing After Allogeneic Stem Cell Transplant (clinicaltrials.gov) - P2 | N=55 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed

Trial completion • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

SYNERGISTIC ANTIPROLIFERATIVE AND PRO-APOPTOTIC EFFECTS OF EPIGENETIC DRUGS GUADECITABINE AND DOMATINOSTAT IN PLEURAL MESOTHELIOMA CELLS (CHEST 2024) - "In conclusion, the combination treatment of gDAC and domatinostat at low and clinically well tolerated doses exhibited a synergistic activity in inducing anti-proliferative and pro-apoptotic effects in PM cell line MPP89. Further research is needed to validate our in vitro findings in vivo and explore the mechanisms underlying the synergistic effects of domatinostat and gDAC in PM cells. CLINICAL IMPLICATIONS: This study contributes to addressing the urgent need for novel therapeutic approaches in PM and suggests the potential clinical utility of gDAC and domatinostat combination treatment in PM patients."

Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Sarcoma • Solid Tumor

The effect of pre-partum shearing of Corriedale ewes on placental and lamb development and neonatal behaviour. (PubMed, N Z Vet J) - "At 70 days of gestation, 37 multiparous Corriedale ewes with known gestation dates were randomly allocated into three groups: S70 (n = 12) and S110 (n = 12), shorn at Day 70 and 110 of gestation, and US (n = 13), that were not shorn pre-partum...Shearing ewes pre-partum may lead to placental changes affecting lamb development and behaviour and associated with higher survival. The findings suggest pre-partum shearing may improve lamb survival, farm profitability and sustainability."

Journal

Impact of whole-body vibration training on ankle joint proprioception and balance in stroke patients: a prospective cohort study. (PubMed, BMC Musculoskelet Disord) - "This study demonstrates that WBV therapy is equally effective as conventional methods in enhancing proprioception and balance in stroke patients, but it does not provide additional benefits for balance recovery. WBV significantly improves proprioceptive functions, particularly in DP and IE parameters. However, it does not surpass traditional rehabilitation methods in terms of balance recovery. These findings indicate that WBV should be incorporated into stroke rehabilitation primarily to enhance proprioception rather than to optimize balance recovery."

Clinical • Journal • Cardiovascular • CNS Disorders

Nivolumab plus ipilimumab and ASTX727 or nivolumab plus ipilimumab in PD-1 resistant metastatic melanoma: Primary analysis of the randomized phase II NIBIT-ML1 study (ESMO 2024) - P2 | "Background: We had shown that the hypomethylating agent (HMA) guadecitabine (guad), a prodrug of decitabine (D), followed by ipilimumab (I) is safe, with promising clinical and immune-modulating activity in metastatic melanoma (MM) patients (pts) (Di Giacomo, CCR 2019; Noviello, Nature Comm 2023). Treatment with ASTX727 plus I+N is feasible, safe, with meaningful clinical activity in PD-1 refractory MM pts."

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

Dysregulation of mitochondria, apoptosis and mitophagy in Leber's hereditary optic neuropathy with MT-ND1 3635G>A mutation. (PubMed, Gene) - "The disruption of electrostatic interactions among S110 of the MT-ND1 and the side chain of E4, along with the carbonyl backbone of M1 in the NDUFA1, was observed in complex I of cybrids with m.3635G>A...Overall, the current study has confirmed the crucial involvement of the alteration of the m.3635G>A gene in the development of LHON. These findings contribute to a deeper comprehension of the pathophysiological mechanisms underlying LHON, providing a fundamental basis for further research."

Journal • Genetic Disorders • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • CASP3 • CASP7 • CASP9

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 2024 ➔ Jul 2025 | Trial primary completion date: Jul 2024 ➔ Jul 2025

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

NCI-2014-02377: Guadecitabine in Treating Patients With Higher-Risk Myelodysplastic Syndromes (clinicaltrials.gov) - P2 | N=100 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed | N=71 ➔ 100 | Trial completion date: Nov 2024 ➔ Jul 2024 | Trial primary completion date: Nov 2024 ➔ Jul 2024

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

Bonding Effectiveness of Veneering Ceramic to Zirconia after Different Grit-Blasting Treatments. (PubMed, Dent J (Basel)) - "Pre-S-30, Pre-S-50, and Pre-S-110 were grit-blasted with 30-µm SiO2-coated Al2O3, 50-µm Al2O3 and 110-µm Al2O3 particles, respectively, before sintering...Grit-blasting with 30-µm SiO2-coated Al2O3 after sintering improved bonding of the veneering ceramic to zirconia. Clinical Significance: As grit-blasting with 30-µm SiO2-coated Al2O3 after sintering improved bonding of the veneering ceramic to zirconia, it may reduce veneering ceramic fractures/chipping."

Journal • Musculoskeletal Diseases • Orthopedics