P2, N=48, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

AZD1332 and AZD7762 were more effective for patients in the low-risk group, whereas Entinostat, Nilotinib, Ruxolutinib, and Wnt.c59 were more effective for patients in the high-risk group. Knockdown of TYMS significantly inhibited the proliferation and invasive ability of ESCC cells in vitro. Overall, our MAR model provides stable and reliable results and may be used as a prognostic biomarker for personalized treatment of patients with ESCC.

P1/2, N=28, Recruiting, Henan Cancer Hospital | Trial primary completion date: Feb 2024 --> Jun 2024

Class I HDACi (VK1, entinostat) showed the same toxicity profile as the pan-HDACi vorinostat. We identify the induction of ferroptosis as new mechanism of action of class I HDACi in gastric cancer. Notably, these findings were independent of the genetic background of the cell lines, thus introducing HDAC inhibition as a more general therapeutic principle.

P2, N=143, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=101 --> 143

P2, N=60, Not yet recruiting, Chinese PLA General Hospital

P2, N=19, Completed, 4SC AG | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Feb 2024

P=N/A, N=184, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

Chidamide can inhibit HDAC activity in MSC, upregulate the expression of the osteogenic transcription factor RUNX2, and promote the osteogenic differentiation of MDS-MSC.

P1/2, N=107, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025

Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.

This study confirmed that the combination of histone deacetylase (HDAC) inhibitors and androgen receptor (AR) antagonists possessed greater therapeutic efficacy than monotherapy in LAR TNBC. This finding significantly bolsters the theoretical basis for the clinical translation of this combination therapy and provides an innovative strategy for the targeted treatment of LAR TNBC.

P3, N=107, Recruiting, Peking Union Medical College Hospital | Not yet recruiting --> Recruiting | Trial primary completion date: Oct 2023 --> May 2024

NCOR1::GLYR1 gene is considered as the pathogenic factor for the MDS/MPN patient with neutropenia.

6c (chlopynostat) was identified as a potent HDAC1i with a superior profile over entinostat...To sum up, HDAC1 inhibition is necessary to reactivate STAT4/p66Shc expression in patients with CLL. 6c is one of the most potent HDAC1is known to date and represents a novel pharmacological tool for reversing the impairment of the STAT4/p66Shc apoptotic machinery.

Here, we identify class I histone deacetylase inhibitors (HDACi) as boosters of CAR-T cell function by high-throughput screening of chromatin-modifying drugs, in which M344 and chidamide enhance memory maintenance and resistance to exhaustion of CAR-T cells that induce sustained antitumor efficacy both in vitro and in vivo...Multi-omics analyses from RNA-seq, ATAC-seq, and H3K27ac CUT&Tag-seq show that HDACi upregulate expression of TCF4, LEF1, and CTNNB1, which subsequently activate the canonical Wnt/β-catenin pathway. Collectively, our findings elucidate the functional roles of class I HDACi in enhancing CAR-T cell function, which provides the basis and therapeutic targets for synergic combination of CAR-T cell therapy and HDACi treatment.

P2, N=58, Active, not recruiting, National Cancer Institute (NCI)

Our data have demonstrated chidamide combined with matrine to exhibit elevated antitumor activity in both CTCL cells and xenograft models of NOD/SCID mice, which may be a potential treatment option for CTCL.

In conclusion, our data suggest that HBI-8000 inhibits fibrosis by modulating the TGF-β1/MAPK pathway thereby improving HFpEF. Therefore, HBI-8000 may become a new hope for the treatment of HFpEF patients.

P1, N=28, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P1b --> P1 | Trial completion date: Jun 2023 --> Mar 2025

Among them, compound B7 exhibited significantly higher antiproliferative activity in the MV411 cell line compared to the positive control, tucidinostat...Further mechanistic studies indicated that compound B7 induced apoptosis through the Caspase-3 pathway in MV411 cells and enhanced histone acetylation levels in the MV411 cell line. These findings highlight the broad potential application of these arctigenin derivatives in cancer therapy.

It can also improve the abnormal DLBCL microenvironment in which immune escape occurs, and inhibit immune escape. This study provides a new therapeutic idea for the exploration of individualized precision therapy for patients with malignant lymphoma.

A quantitative proteomic analysis of MCs treated with MS-275, an HDAC1-3 inhibitor, unveiled altered expression of several proteins, including inflammatory cytokines/chemokines and interferon-stimulated genes (ISGs)...Collectively, our findings underline the significance of viral infections in acquiring a mesenchymal-like phenotype by MCs and the potential consequences of virus-associated peritonitis episodes for PD patients. The observed promotion of MMT reversal and interferon response inhibition by an HDAC1-3 inhibitor, albeit without a general impact on inflammatory cytokine production, has translational implications deserving further analysis.

This study provided real-world data for the use of chidamide in patients with HoR-positive and HER2-negative MBC. Our data endorsed the use of chidamide in patients pretreated with CDK4/6 inhibitors and patients treated with different endocrine combinations.

Despite the rate of PEPI score 0 was not high, tucidinostat plus exemestane as a neoadjuvant therapy might be well tolerated and showed promising clinical responses in patients with early hormone receptor-positive, HER2-negative breast cancer. To clarify the safety and efficacy of this strategy, further investigation is warranted.

In the randomized phase 2 CAPability-01 trial, we investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Our study suggests that the combination of a PD-1 antibody, an HDACi, and a VEGF antibody could be a promising treatment regimen for patients with MSS/pMMR advanced colorectal cancer. ClinicalTrials.gov registration: NCT04724239 .

Furthermore, we identified an effective synergistic combination between anwulignan and chidamide. Our findings suggested that PIM1 could be a therapeutic target and prognostic factor for DLBCL, and anwulignan holds promise for future development as a natural product for treatment.

P2, N=33, Recruiting, Great Novel Therapeutics Biotech & Medicals Corporation | Not yet recruiting --> Recruiting

Chidamide also alleviated tumor immunosuppression by reducing the number of M-MDSCs in LLC-bearing mice, thereby enhancing the antitumor efficacy of gefitinib. In conclusion, our findings suggest that chidamide can improve gefitinib treatment outcomes, indicating that MDSCs are promising targets in NSCLC.

P2, N=21, Active, not recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

The findings of this study provide a compelling justification for the clinical utilization of chidamide and orelabrutinib to treat relapsed/refractory DLBCL.

Eleven out of 329 selected flavonoids were screened based on molecular docking studies, as they have higher binding affinities than the standard drugs vorinostat and panobinostat. Further experimental validation is needed to understand the selectivity of flavonoids as HDAC2 inhibitors. The online version contains supplementary material available at 10.1007/s13205-023-03912-5.

P1/2, N=91, Recruiting, University Hospital Heidelberg | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Jun 2024 --> Jun 2026

There remains a need for postoperative adjuvant drug therapy for the subpopulation of breast cancer patients with high-risk residual cancer after curative therapy. This trial is registered with NCT03473639.

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.

In this work, we designed PCPA-entinostat conjugates for selective cancer cell targeting. PCPA-entinostat conjugate 12 with a 4-oxybenzyl group linker released entinostat in the presence of LSD1 in in vitro assays and selectively inhibited the growth of cancer cells in preference to normal cells, suggesting the potential of PCPA-entinostat conjugates as novel anticancer drug delivery small molecules.

Combining ADCT-602 + pacritinib was beneficial in ADCT-602-resistant cells. Chidamide increased CD22 expression on B-cell tumor surfaces, increasing ADCT-602 activity. These data support clinical testing of ADCT-602 in R/R B-ALL (NCT03698552) and CD22-positive hematological cancers.

Thus, we identified the function of the CYLD-HDAC axis in radiotherapy and blocking HDACs by Chidamide can increase the sensitivity of cancer cells and tumors to radiation therapy both in vitro and in vivo. In addition, ChIP and luciferase reporter assays revealed that CYLD could be transcriptionally regulated by zinc finger protein 202 (ZNF202). Our findings offer novel insight into the function of CYLD in tumor and uncover important roles for CYLD-HDAC axis in radiosensitivity, which provide new molecular target and therapeutic strategy for tumor radiotherapy.

Our study unveils a direct impact of HDAC-1/2 in the regulation of MC/EOC adhesion and highlights the regulation of MC plasticity by epigenetic inhibition as a potential target for therapeutic intervention in EOC peritoneal metastasis.

P2, N=67, Recruiting, Nanfang Hospital, Southern Medical University

P2, N=32, Recruiting, The First Affiliated Hospital of Soochow University

P1/2, N=44, Recruiting, Biyun Wang, MD | Trial completion date: May 2023 --> May 2025 | Trial primary completion date: Feb 2023 --> Feb 2025