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

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

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

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.

Moreover, SPARC upregulation due to HDAC10 depletion partly accounts for the resensitization of resistant cells to a BRAF inhibitor. Our work reveals the role of HDAC10 in gene regulation through indirect histone modification and suggests a potential therapeutic strategy for melanoma or other cancers by targeting HDAC10 and SPARC.

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.

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.

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.

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.

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.

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.

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

P=N/A, N=50, Recruiting, The First Affiliated Hospital with Nanjing Medical University

First, a combination of an AR inhibitor (enzalutamide, Enz) and a selective histone deacetylase inhibitor (chidamide, Chid) was used to treat AR‑positive TNBC cell lines, and a synergistic effect of these drugs was observed. In conclusion, the results of the present study revealed that combination treatment with Enz and Chid can upregulate IRS4, which results in the blocking of KRAS signalling and suppression of tumour growth. It may be hypothesised that the expression levels of IRS4 could be used as a biomarker for screening patients with AR‑positive TNBC using Enz and Chid combination therapy.

In all, 52.17% patients were treated with tucidinostat plus fulvestrant, while 38.30% were treated with tucidinostat plus aromatase inhibitors. For patients with HR/HER2 ABC, tucidinostat combination therapy offers certain survival benefits with controllable safety. Furthermore, compared with non-maintenance therapy, maintenance therapy after chemotherapy may have promising efficacy.

Alterations of HDAC genes, including enhanced expression and mutations, are positively related to DLBCL. Targeting HDACs with specific inhibitors such as Chidamide may represent a potential therapeutic approach for DLBCL patients.

P2, N=74, Recruiting, Sun Yat-sen University | N=53 --> 74