Jingzhuda (entinostat) / Syndax Pharma, EOC Pharma, Edding Genor Group - LARVOL DELTA

Pathologic response and safety of neoadjuvant pembrolizumab with or without entinostat in muscle-invasive urothelial cancer (MIUC). (ASCO 2025) - P2 | "Neoadjuvant pembrolizumab with or without entinostat is active in MIUC with an acceptable safety profile. Analysis of the primary endpoint and other translational endpoints is ongoing."

Clinical • IO biomarker • Back Pain • Fatigue • Genito-urinary Cancer • Heart Failure • Musculoskeletal Pain • Oncology • Pain • Solid Tumor • Urothelial Cancer • HDAC1

ETCTN-9844: Entinostat, Nivolumab, and Ipilimumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Locally Advanced or Metastatic HER2-Negative Breast Cancer (clinicaltrials.gov) - P1 | N=57 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2026 ➔ Sep 2027

Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Orthotopic PDX modeling and preclinical therapeutic evaluation in pediatric ependymoma (EANO 2026) - "A targeted drug panel based on molecular alterations in ST-EPN, including CBL0137 (epigenetic inhibitor), ACT001 (NF-κB inhibitor), dovitinib and lenvatinib (VEGFR inhibitors), and entinostat and quisinostat (HDAC inhibitors) was evaluated for cytotoxicity in vitro using Alamar Blue and clonogenic assays. These orthotopic ST-EPN PDX models represent a reliable preclinical platform, enabling evaluation of molecularly guided combination therapies for pediatric ST-EPN with ZFTA-RELA fusion. Dovitinib emerged as a potential new treatment for RELA fused EPN."

Preclinical • Ependymoma • Oncology • Solid Tumor • RELA • ZFTA

Comprehensive genomic and transcriptomic analyses capture the effects of epigenetic therapy priming on immune checkpoint blockade response in non-small cell lung cancer (AACR 2024) - P2 | "Here we employed a multi-omic approach to understand the effects of epigenetic priming in re-shaping the tumor microenvironment, together with genomic drivers of therapeutic response of epigenetic therapy followed by ICB in non-small cell lung cancer (NSCLC). We performed whole exome sequencing (WES) on 39 baseline tumors and bulk RNA sequencing (RNAseq) on 18 serial tumors across 42 patients with metastatic immunotherapy-naïve NSCLC, who received azacitidine and entinostat followed by nivolumab (NCT01928576). Genomic and transcriptomic analyses reveal the potential of epigenetic-priming to re-shape the tumor microenvironment and highlight patients that could benefit from combination epigenetic therapy with immunotherapy."

Checkpoint block • Checkpoint inhibition • IO biomarker • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IFNG • MAGEA10 • MAGEB2 • TMB

Histone Deacetylase Inhibitors Improve Memory Function and Decrease Neuropathology in APP/PS1 Mice. (PubMed, Res Sq) - "CI-994 primarily targets hippocampal synaptic plasticity to improve long-term spatial memory, whereas MS-275 preferentially modulates PFC synaptic function and reduces amyloid pathology, leading to improved recognition and working memory. Together, these results identify region-specific HDAC mechanisms that differentially regulate cognitive function and AD pathology, supporting selective HDAC inhibition as a promising therapeutic strategy for AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders

Phase I/II Evaluation of the Combination of Entinostat, M9241 and Bintrafusp Alfa in Patients with Advanced HPV Related Malignancies (SITC 2022) - P1/2 | "Background More than 630,000 cases of HPV related cancer (e.g. cervical, oropharyngeal, anal) occur worldwide annually. To date the triple combination appears to have a manageable safety profile along with encouraging clinical activity in patients with advanced checkpoint refractory HPV related cancers including in pts who have previously progressed on PD(L)1 inhibitor then on PDS0101, M9241 and bintrafusp alfa. Trial Registration NCT04708470"

Clinical • P1/2 data • Cervical Cancer • Oncology • Oropharyngeal Cancer • IL12A • STAT3 • TGFB1

CpG hypermethylation and WNT/AP-1 cooperativity define the epigenetic landscape and a clinical subgroup of high-risk pediatric adrenocortical carcinoma. (PubMed, Nat Commun) - "Mechanistically, the histone deacetylase inhibitor entinostat reverses promoter methylation, silences activator protein-1 activity, and induces apoptotic reprogramming in tumor models. These findings establish a molecular framework for risk stratification and identify actionable therapeutic vulnerabilities, providing an essential resource for studying this molecularly uncharted pediatric malignancy."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Pediatrics • Solid Tumor

Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial. (PubMed, Nat Cancer) - P1 | "Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial."

IO biomarker • Journal • Metastases • P1 data • Tumor mutational burden • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • FOXP3 • HER-2 • PD-L1 • TMB

Phase I Study of Entinostat, Atezolizumab, Carboplatin, and Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer, ETCTN 10399. (PubMed, Oncologist) - P1 | "Addition of entinostat to atezolizumab, carboplatin, and etoposide is unsafe and resulted in early onset and severe neutropenia, thrombocytopenia. Further exploration of entinostat with carboplatin, etoposide, and atezolizumab should not be explored. (ClinicalTrials.gov Identifier: NCT04631029)."

Journal • P1 data • Endocrine Disorders • Febrile Neutropenia • Hematological Disorders • Infectious Disease • Leukopenia • Lung Cancer • Neuroendocrine Tumor • Neutropenia • Oncology • Septic Shock • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • CREBBP • EP300

Epigenetic plus cytokine therapy induces stem-like CD8+ T-cell reservoirs and intratumoral immune niches to overcome anti-PD-1 resistance. (PubMed, J Immunother Cancer) - "Treatment with entinostat, N-803, and αPD-1 boosts anti-tumor intratumoral immune niches comprising TCF1+CD8+ T cells. Collectively, these findings suggest that TCF1+CD8+ T cell immune niches previously associated with αPD-1 responsiveness and lacking in non-responders, including most CRC patients, may be restored by the addition of entinostat and N-803 to αPD-1 therapy to treat αPD-1-refractory patients."

IO biomarker • Journal • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD8 • GZMB

Fulzerasib combined with HDAC inhibitors (Entinostat) and Vitamin E succinate in KRASG12C lung cancer cell lines (ESMO 2026) - No abstract available

Preclinical • Lung Cancer • Oncology • Solid Tumor • KRAS

Immunomodulation of the tumor microenvironment of pancreatic ductal adenocarcinoma with histone deacetylase inhibition: Results of a phase 2 clinical trial of entinostat in combination with nivolumab (AACR 2024) - "Paired tissue and peripheral analysis showed immunomodulation of myeloid cell populations, consistent with the preclinical hypothesis supporting the trial. This study creates a roadmap for this strategy with future combinatorial therapeutic approaches to enhance the clinical benefit in PDA patients further."

Biomarker • Clinical • Combination therapy • Epigenetic controller • Immunomodulating • IO biomarker • P2 data • Tumor microenvironment • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Phase I Trial of Regorafenib, Hydroxychloroquine, and Entinostat in Metastatic Colorectal Cancer. (PubMed, Oncologist) - P1/2 | "The combination of regorafenib, HCQ, and entinostat was poorly tolerated without evident activity in metastatic CRC."

Journal • P1 data • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Oncology • Solid Tumor

Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial. (PubMed, Nat Commun) - P2 | "Although the primary endpoint was not met, entinostat and nivolumab showed durable responses in a small subset of PDA patients. Myeloid cell immunomodulation supported the preclinical hypothesis, providing a basis for future combinatorial therapies to enhance clinical benefits in PDA."

Combination therapy • IO biomarker • Journal • Metastases • P2 data • Cardiovascular • Heart Failure • Hematological Disorders • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Melanoma to rhabdomyosarcoma plasticity in the setting of immunotherapy. (PubMed, Med) - "This case provides molecular evidence of phenotypic plasticity occurring under the selective pressure of immune checkpoint inhibitor therapy."

IO biomarker • Journal • Melanoma • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • CD163 • NF1 • NRAS

Integration of Bulk RNA Sequencing and Single-Cell Sequencing to Identify Prognostic Genes Associated With MCDRGs in Neuroblastoma. (PubMed, FASEB J) - "Ribosome biogenesis and cell cycle-related pathways were enriched in the HRG, which displayed higher sensitivity to entinostat and sapitinib. This model systematically reveals the comprehensive mechanisms by which MCDRGs influence prognosis through regulating the TME, cell-cell interactions, and therapeutic responses. These findings provide a new theoretical basis and potential targets for precise risk stratification and individualized treatment strategies in NB."

Biomarker • Journal • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • TRIB1

Immune Circuit Rewiring by HDAC Inhibition Enables Response to Dual Checkpoint Blockade in Metastatic Breast Cancer. (PubMed, Cancer Res) - "Analyses of patient biopsies and blood via spatial proteomics and flow cytometry corroborated the preclinical findings, showing increased T cell and B cell activation, mature tertiary lymphoid structures, and increased CD8+ T cell-macrophage distances in responders to entinostat + nivolumab + ipilimumab. Mathematical modeling of tumor-immune dynamics implicated simultaneous modulation of multiple TME interactions as required for response to the combination treatment. Overall, this study identifies lymphoid and myeloid cell contributions to response to treatment with HDAC inhibitors and immune checkpoint blockade, providing a framework for discovering interactions driving responses in complex TMEs."

Checkpoint inhibition • Journal • Breast Cancer • Oncology • Solid Tumor • CD8 • ICAM1 • IFNG

A Derivatization-Free Parallel Reaction Monitoring-Based Proteomics Workflow for Quantitative, Site-Specific Analysis of Histone Post-Translational Modifications. (PubMed, ACS Omega) - "To illustrate its utility, we analyzed PTM dynamics in cells expressing histone H3.3 lysine-to-methionine substitutions and in cells treated with the histone deacetylase inhibitor entinostat, yielding results that correlated strongly with antibody-based readouts. This PRM platform provides a complementary, targeted approach to current chemical derivatization-based methods, enabling reliable validation of selected histone PTMs."

Journal

Histone deacetylase inhibitors enhance the amoebicidal activity of amphotericin B against Naegleria fowleri. (PubMed, Int J Parasitol Drugs Drug Resist) - "Class-specific HDACis, including class I inhibitors MS275 and MGCD0103 and a class II inhibitor MC1568, showed minimal effects on trophozoite viability...These combination treatments also exhibited low cytopathic effects on human brain tumor cells. These findings suggest that SAHA and JNJ, particularly in combination with AmB, hold promise as therapeutic candidates against N. fowleri infection while potentially mitigating the severe side effects associated with AmB."

Journal • Brain Cancer • CNS Disorders • Infectious Disease • Oncology • Solid Tumor

Entinostat and Tucidinostat Potentiate Temozolomide Response in Glioblastoma Models. (PubMed, Pharmazie) - "Entinostat and Tucidinostat enhance TMZ sensitivity in GBM models and are associated with specific markers and morphological changes that persist despite HDAC1/2/3 knockout. These findings support further evaluation of Entinostat and Tucidinostat as TMZ-sensitizing agents in GBM models and highlight associated phenotypic and molecular changes that warrant further mechanistic validation."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • FAP • GFAP • HDAC1 • TUBB3

Histone Deacetylase Inhibitor Combined with Rosiglitazone Improves Cognitive Function Via Microglial Polarization and Increased Mature/Pro-BDNF in Alzheimer's Disease. (PubMed, Adv Pharm Bull) - "Forty adult male Wistar rats were randomly assigned into five groups (n=8 per group): (1) Control group receiving saline, (2) AD model group (induced by i.c.v injection of Streptozocin), (3) AD+Rosiglitazone (ROSI) (4) AD+MS-275, and (5) AD+combined ROSI and MS-275 group. Also an increased mature brain-derived neurotrophic factor (BDNF)/pro-BDNF ratio was found in treated groups compared with STZ+saline (P<0.001). These findings suggest that co-administration of Rosiglitazone and MS-275 improves cognitive function in AD rats, potentially through shifting microglial polarization from the M1 to the M2 phenotype and enhancing synaptic strength via an increased mature BDNF/pro-BDNF ratio."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Solid Tumor • BDNF

Stepwise Enhancement of HPV16 E6/E7 mRNA Vaccine Efficacy Using HSV-1 gD Epitope Incorporation and Immune-Modulating Agents. (PubMed, Res Sq) - "Antitumor efficacy, antigen-specific T-cell responses, and tumor immune infiltration were assessed following vaccination alone or in combination with the histone deacetylase (HDAC) inhibitor entinostat or the STING agonist ADU-S100, two immunomodulatory agents known to remodel the tumor microenvironment. These findings demonstrate that incorporation of a heterologous HSV-1 gD helper epitope can augment HPV E6/E7-targeted mRNA vaccination by harnessing pre-existing HSV-1-specific immune memory and enhancing CD4⁺ T-cell help. Together with ubiquitin-mediated enhancement of antigen presentation and modulation of the tumor microenvironment through HDAC inhibition or STING activation, these complementary potentiation strategies may further improve therapeutic outcomes and support the development of combinatorial immunotherapeutic approaches for HPV-associated cancers."

Journal • Herpes Simplex • Infectious Disease • Oncology • Targeted Protein Degradation • CD4 • CD8

Three High Throughput Compatible Cell-Based Assays for Identifying Small Molecule JAG1 Upregulators for Alagille Syndrome. (PubMed, SLAS Discov) - "Entinostat, Mocetinostat, and Chidamide were consistently identified as the most potent JAG1 upregulators across all assays. These complementary assays provide a flexible platform for identifying small molecule modulators of gene dosage and may be broadly applicable to drug discovery efforts targeting haploinsufficiency diseases."

Journal • JAG1

Combination Therapy With Entinostat and Pembrolizumab in Relapsed and Refractory Lymphomas (clinicaltrials.gov) - P2 | N=47 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • CTLA4

Exemestane With or Without Entinostat in Treating Patients With Recurrent Hormone Receptor-Positive Breast Cancer That is Locally Advanced or Metastatic (clinicaltrials.gov) - P3 | N=608 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR