decitabine

The combination of DAC/αPD-L1 shows promise in improving HBV-specific T cell responses in vitro, highlighting the potential of remodeling exhaustion-associated epigenetic signatures to enhance HBV-specific T cell restoration and suggesting a novel immunotherapeutic avenue for CHB.

P1/2, N=122, Completed, BerGenBio ASA | Active, not recruiting --> Completed

P2, N=20, Recruiting, Beijing 302 Hospital

The most well-studied and clinically advanced epigenetic-targeted therapies include azacitidine and decitabine, which inhibit DNA methylation through competitive inhibition of the enzymatic activity of the DNA methyltransferase family enzymes. Small molecules that disrupt oncogenic fusion protein activity and their associated chromatin complexes have demonstrated remarkable promise, and this approach has become the standard treatment for a subset of leukemias driven by the PML-RARA oncogenic fusion protein. A deeper understanding of the mechanisms that drive epigenetic dysregulation in pediatric cancer may hold the key to future success in this field, as the landscape of druggable epigenetic targets is also expanding.

Our report sheds light on the distinct clinical presentations of ET patients who develop AML, characterized by different TP53 mutations and varying therapeutic outcomes when treated with decitabine. However, further studies that include a larger quantity of samples are needed to elucidate the precise underlying molecular mechanisms involved in this process.

P1/2, N=218, Active, not recruiting, AbbVie | Trial completion date: Dec 2024 --> Apr 2026 | Trial primary completion date: Dec 2024 --> Apr 2026

P1, N=29, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jan 2024 --> Jun 2025

P3, N=727, Completed, ECOG-ACRIN Cancer Research Group | Active, not recruiting --> Completed

P1/2, N=6, Active, not recruiting, Thomas Jefferson University | Recruiting --> Active, not recruiting | N=37 --> 6

The SRHLS sequentially released decitabine and STING agonists, thereby correcting STING signaling dysfunction through epigenetic reprogramming and enhancing antitumor immunity. According to in vitro and in vivo experiments, the SRHLS reshaped the tumor microenvironment and markedly inhibited tumor growth, recurrence, and metastasis. These findings underscore the potential of the SRHLS as a promising therapeutic strategy for GBM.

P2/3, N=76, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

Here, we utilized polymeric hydrogel loaded with decitabine (DAC), cisplatin (CDDP) and manganese ions (Mn2+) as a postoperative filler immunogel to synergistically activate both anti-tumor innate and adaptive immunity. Such immunogel achieved an encouraging anti-tumor effect with an 80 % total survival rate for recurrent tumors and a 60 % survival rate for metastatic tumors. Considering that this in situ immunogel possesses simple formulation and displays superior anti-tumor effect, this research provided a promising strategy for postoperative cancer therapy.

P1, N=32, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=54 --> 32

P2, N=28, Not yet recruiting, Seoul National University Hospital

Low expression of GREM2 in breast cancer cells is associated with hypermethylation of the GREM2 promoter, which may ultimately contribute to poor patient survival. GREM2 participates in regulating the expression of various genes, including ID1, and is involved in suppressing the proliferation of breast cancer cells. This suggests that GREM2 has the potential to act as a novel tumor suppressor in breast cancer.

DAC treatment increased immunogenicity and decreased proliferation in HNSCC cells while enhancing expression of co-stimulatory ICM GITR and OX40. We propose low dose DAC treatment as a adjuvant to immunotherapy.

P2, N=37, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Initiation date: Jun 2024 --> Nov 2024

Ferroptosis analysis indicated that ALOX5 and VLDLR were the top CAPG-related ferroptosis markers; glutathione metabolism levels in tumor group were generally high, and decitabine was a ferroptosis inducer...Moreover, four chemotherapy drugs showed better sensitivity to UCEC patients in the low-risk cohort. CAPG may serve as a potential biomarker of UCEC owing to its role in modulating the immune response and ferroptosis, providing novel perspectives for combined immunotherapy of UCEC.

The combination of sintilimab and decitabine shows promise efficacy for higher-risk MDS, with a favorable safety profile. The potential predictive value of T cell exhaustion biomarkers might help screen the possible benefiting population.

P2, N=49, Recruiting, Ruijin Hospital

P2, N=30, Recruiting, The First Affiliated Hospital of Soochow University | Not yet recruiting --> Recruiting

Finally, we highlight some of the ongoing studies that test quizartinib in patients with FLT3-ITD-positive AML, patients with FLT3-ITD-negative AML, in both the first-line and R/R settings, in patients fit or unfit for intensive chemotherapy, including studies for quizartinib-based combination with other compounds such as decitabine and venetoclax. Future research should aim to further optimize the clinical value of quizartinib and explore its use in additional clinical settings, which could be achieved by testing quizartinib with other drugs, better characterization of the mechanisms of resistance, identification of the role of quizartinib as a maintenance therapy after allo-HCT, and investigating quizartinib in patients with FLT3-ITD-negative AML.

P1/2, N=20, Not yet recruiting, Benjamin Tomlinson | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=75, Completed, University of Nebraska | Active, not recruiting --> Completed | Trial primary completion date: Oct 2024 --> Mar 2024

P2, N=59, Recruiting, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

P=N/A, N=76, Recruiting, Ningbo First Hospital; Ningbo First Hospital

P2, N=101, Active, not recruiting, Gruppo Italiano Malattie EMatologiche dell'Adulto | Recruiting --> Active, not recruiting | Trial completion date: May 2024 --> Apr 2026 | Trial primary completion date: May 2024 --> Oct 2024

P1, N=20, Recruiting, Benjamin Tomlinson | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

SYNE1 contributes to the modulation of sorafenib resistance in ccRCC cells through interacting with BIN1. Decitabine treatment enhances expressions of these two proteins to improve TKI response, suggesting a potential strategy for counteracting resistance and bettering patient outcomes.

Herein, an injectable hydrogel-encapsulated autocatalytic copper peroxide (CP@Gel) therapeutic platform is designed and combine it with the clinical-grade DNA methyltransferase inhibitor decitabine (DAC) to effectively inhibit TNBC growth and postoperative recurrence via pyroptosis, killing residual cancer cells that bypass apoptosis resistance while also improving immunogenicity and modulating immunosuppression to achieve an intense anti-tumor immune response...The in vivo results show a 67% elimination of local tumor recurrence via treatment with DAC+CP@Gel, suggesting the successful integration of sustained drug release with autocatalysis and epigenetic modification. The results thus suggest great potential for pyroptosis-based and injectable hydrogel-aided strategies for preventing the postoperative recurrence of TNBC.

P2, N=76, Recruiting, Ruijin Hospital | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=18, Recruiting, The First Affiliated Hospital of Xiamen University

Objective: To investigate the efficacy and prognosis of CLAG±DAC (Clofarabine, Cytarabine, G-CSF±Decitabine) chemotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) . The remission rate was relatively higher in patients with R/R AML combined with FLT3-ITD mutation by applying the DAC+CLAG regimen (OR=10.84, 95%CI 1.48-288.50, P=0.04) . The CLAG±DAC regimen is considered effective in patients with R/R AML, whereas decitabine combined with the CLAG regimen is more suitable for patients with R/R AML combined with FLT3-ITD mutation.

Furthermore, DAC + DOX@FPSD NP treatment could promote pyroptosis-associated antitumor immunity, as evidenced by the increased presence of CD3+, CD4+, and CD8+ T cells, heightened secretion of tumor necrosis factor-α and interferon-γ, elevated high-mobility group box-1 levels, and enhanced calreticulin exposure. The FPSD nanocarrier developed in this study had favorable stability, active targeting ability, biocompatibility, and controlled release properties, and the DAC + DOX@FPSD NPs represented an approach to antitumor therapy by inducing pyroptosis, which offers a promising avenue for breast cancer treatment.

Our findings advanced the mechanistic understanding of variations in PER3 expression in cancers and confirmed the tumor-associated function of PER3 hypermethylation and downregulation.

In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. Further studies of ATRA combined with hypomethylating agents appear warranted in non-M3 AML patients ineligible for HMA/venetoclax therapy. Trial Registration: ClinicalTrials.gov identifier: NCT00867672.

In the decitabine plus midostaurin arm 24% reached CR/CRi, the median OS was 4.8 months and 1-yrs OS was 31% which compared with 34% CR/CRi, median OS of 7.4 months and 1-yrs OS of 37% for the decitabine alone group (NS). Thus, while the addition of midostaurin appears safe, it does not enhance therapeutic efficacy of decitabine in unfit AML patients.

P2, N=39, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

Future research should incorporate larger sample sizes and advanced genomic techniques like RNA sequencing to better understand oncogenic mechanisms. The study emphasizes the need for further in situ analyses of decitabine's efficacy, setting the foundation for future neuro-oncological treatments.

A metronomic, low-dose schedule of decitabine and Venetoclax was safe and effective in myeloid malignancies with few dose reductions or interruptions in an older diverse population. Median OS for AML and TP53 mutated patients was 16.1 and 11.3 months respectively.

The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

The combination of decitabine, venetoclax, and ponatinib is safe and shows promising activity in patients with advanced phase chronic myeloid leukaemia, including those with multiple previous therapies or high-risk disease features. Further studies evaluating chemotherapy and venetoclax-based combination strategies using newer-generation BCR::ABL1 tyrosine kinase inhibitors are warranted.