- |||||||||| Piqray (alpelisib) / Novartis, JQ-1 / Roche, entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax Pharma
Journal, IO biomarker: The novel dual BET/HDAC inhibitor TW09 mediates cell death by mitochondrial apoptosis in rhabdomyosarcoma cells. (Pubmed Central) - Jan 28, 2021
This results in BAK and BAX activation and caspase-dependent apoptosis, since individual genetic silencing of BIM, NOXA, PUMA, BMF, BAK or BAX, overexpression of BCL-2 or the caspase inhibition with zVAD.fmk all rescue JQ1/BYL719-induced cell death. In conclusion, TW09 shows potent antitumor activity in RMS cells in vitro by inducing mitochondrial apoptosis and may represent a promising new therapeutic option for the treatment of RMS.
- |||||||||| Jingzhuda (entinostat) / Syndax Pharma, EOC Pharma
Trial completion date, Trial primary completion date, Combination therapy, Epigenetic controller: A Trial to Evaluate Two Schedules of MS275 in Combination With 5AC in Elderly Patients With Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - Jan 26, 2021
P2, N=108, Recruiting,
In conclusion, TW09 shows potent antitumor activity in RMS cells in vitro by inducing mitochondrial apoptosis and may represent a promising new therapeutic option for the treatment of RMS. Trial completion date: Dec 2021 --> Jul 2021 | Trial primary completion date: Dec 2020 --> Jul 2021
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Opdivo (nivolumab) / BMS
Enrollment closed, Trial primary completion date, Combination therapy, Metastases: A Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma (clinicaltrials.gov) - Jan 22, 2021
P2, N=44, Active, not recruiting,
Trial completion date: Dec 2021 --> Jul 2021 | Trial primary completion date: Dec 2020 --> Jul 2021 Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2021 --> Dec 2020
- |||||||||| entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax Pharma
Journal: Synthesis of N-Substituted Benzamide Derivatives and their Evaluation as Antitumor Agents. (Pubmed Central) - Jan 21, 2021
The preliminary SARs showed that (ⅰ) the 2-substituent of the phenyl ring in the R group and heteroatoms of amide which can chelate with zinc ion are critical to the antiproliferative activity and (ⅱ) chlorine atom or nitro-group on the same benzene ring largely decreases their anti-proliferative activity. Molecular docking study illustrated the interaction (binding affinity) between the synthesized compounds and HDAC2 was observed to be similar to that of MS-275.
- |||||||||| entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax Pharma, Opdivo (nivolumab) / Ono Pharma, BMS
Biomarker, Clinical, P1/2 data, Journal, Tumor Mutational Burden, PD(L)-1 Biomarker, IO biomarker: INFORM2 NivEnt: The first trial of the INFORM2 biomarker driven phase I/II trial series: the combination of nivolumab and entinostat in children and adolescents with refractory high-risk malignancies. (Pubmed Central) - Jan 21, 2021
P1/2
It prevents exposure to unnecessary risks by applying the Bayesian adaptive design for early stopping for futility. The adaptive biomarker driven design provides an innovative approach accelerating drug development and reducing exposure to investigational treatments in these vulnerable children at the same time.
- |||||||||| Zolinza (vorinostat) / Merck (MSD), AZD5582 / AstraZeneca, entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax Pharma
Preclinical, Journal: The Intact Non-Inducible Latent HIV-1 Reservoir is Established In an In Vitro Primary T Cell Model of Latency. (Pubmed Central) - Jan 15, 2021
Here we demonstrate the generation of defective, intact and intact non-inducible latent HIV-1 in a T model of latency using different HIV-1 strains. Thus, the mechanisms which control inducibility can be studied using this primary cell model of latency, which may accelerate our understanding of the latent reservoir and the development of curative strategies.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Enrollment change, Trial withdrawal: A Study of Entinostat and FOLFOX in Subjects With Pancreatic Adenocarcinoma (clinicaltrials.gov) - Jan 15, 2021
P1, N=0, Withdrawn,
Thus, the mechanisms which control inducibility can be studied using this primary cell model of latency, which may accelerate our understanding of the latent reservoir and the development of curative strategies. N=24 --> 0 | Not yet recruiting --> Withdrawn
- |||||||||| bintrafusp alfa (M7824) / EMD Serono, PDS01ADC / PDS Biotech, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
New P1/2 trial, Metastases: A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers (clinicaltrials.gov) - Jan 13, 2021
P1/2, N=60, Not yet recruiting,
- |||||||||| bintrafusp alfa (M7824) / EMD Serono, Kadcyla (ado-trastuzumab emtansine) / Roche, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Trial completion date, Trial primary completion date, Metastases: BN-Brachyury, Entinostat, Adotrastuzumab Emtansine and M7824 in Advanced Stage Breast Cancer (BrEAsT) (clinicaltrials.gov) - Jan 13, 2021
P1b, N=65, Recruiting,
N=24 --> 0 | Not yet recruiting --> Withdrawn Trial completion date: Jan 2022 --> Jan 2024 | Trial primary completion date: Jan 2022 --> Jan 2024
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Opdivo (nivolumab) / BMS, Yervoy (ipilimumab) / BMS
Trial primary completion date, PD(L)-1 Biomarker, IO biomarker, Surgery, Metastases: 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) - Jan 5, 2021
P1, N=45, Active, not recruiting,
Entinostat at the selected dose levels in combination with standard dose of enzalutamide showed promising safety profile in this small phase I study. Trial primary completion date: Dec 2020 --> Dec 2021
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Opdivo (nivolumab) / BMS, Yervoy (ipilimumab) / BMS
Enrollment change, Combination therapy: Study of Entinostat With Nivolumab Plus Ipilimumab in Previously Treated Renal Cell Carcinoma (clinicaltrials.gov) - Dec 29, 2020
P2, N=18, Active, not recruiting,
Taken together, these results suggest that HDAC3 inhibition rather than HDAC1/2 inhibition by MS-275 protects against lipotoxicity in C2C12 myotubes and skeletal muscle, and may be effective for the treatment of obesity and insulin resistance. N=53 --> 18
- |||||||||| entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax Pharma
Journal: The Fas/FasL Signaling Pathway: Its Role in the Metastatic Process and as a Target for Treating Osteosarcoma Lung Metastases. (Pubmed Central) - Dec 22, 2020
To this end, we demonstrated that the histone deacetylase inhibitor entinostat upregulated Fas expression on OS cells, reduced their ability to form lung metastases, and induced regression of established micrometastases...We demonstrated that the chemotherapeutic agent gemcitabine (GCB) increased Fas expression in both human and mouse OS cells in vitro...The therapeutic efficacy of GCB was contingent upon a FasL lung microenvironment as aerosol GCB had no effect in FasL-deficient mice. Manipulation of Fas expression and the Fas pathway should be considered, as this concept may provide additional novel therapeutic approaches for treating patients with OS lung metastases.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Stivarga (regorafenib) / Bayer
Trial completion, Enrollment change, Trial completion date, Trial primary completion date, Metastases: To Determine the Safety of Regorafenib, Hydroxychloroquine, and Entinostat Metastatic Colorectal Cancer (clinicaltrials.gov) - Dec 17, 2020
P1/2, N=27, Completed,
These findings thus form the rationale for the use of this combination of agents for patients harboring poorly or non-inflamed solid carcinomas. Suspended --> Completed | N=44 --> 27 | Trial completion date: Jul 2022 --> Jun 2020 | Trial primary completion date: Jul 2021 --> Jun 2020
- |||||||||| bintrafusp alfa (M7824) / EMD Serono, Kadcyla (ado-trastuzumab emtansine) / Roche, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Enrollment open, Metastases: BN-Brachyury, Entinostat, Adotrastuzumab Emtansine and M7824 in Advanced Stage Breast Cancer (BrEAsT) (clinicaltrials.gov) - Nov 26, 2020
P1b, N=65, Recruiting,
Trial primary completion date: Jan 2021 --> May 2020 Not yet recruiting --> Recruiting
- |||||||||| Xtandi (enzalutamide) / Pfizer, Astellas, MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute, entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax Pharma
Journal, PARP Biomarker: Tumor Suppressive Maspin-Sensitized Prostate Cancer to Drug Treatment Through Negative Regulating Androgen Receptor Expression. (Pubmed Central) - Nov 18, 2020
Finally, maspin-mediated repression of AR was induced by treatment of MS-275, which promoted enzalutamide treatment efficacy with decrease of prostate-specific antigen (PSA) expression in LNCaP and 22RV1 cells. Taken together, the data not only demonstrated maspin-mediated repression of AR to augment drug anti-tumor activity but also provided in-depth support for combination of HDAC inhibitors with AR antagonist in CaP therapy.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Tecentriq (atezolizumab) / Roche
New P1 trial, Combination therapy: Testing the Addition of an Anti-cancer Drug, Entinostat, to the Usual Chemotherapy and Immunotherapy Treatment (Atezolizumab, Carboplatin and Etoposide) for Previously Untreated Aggressive Lung Cancer That Has Spread (clinicaltrials.gov) - Nov 17, 2020
P1, N=36, Not yet recruiting,
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Opdivo (nivolumab) / BMS
Trial completion date, Trial primary completion date, Combination therapy, Metastases: A Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma (clinicaltrials.gov) - Nov 12, 2020
P2, N=54, Recruiting,
Taken together, the data not only demonstrated maspin-mediated repression of AR to augment drug anti-tumor activity but also provided in-depth support for combination of HDAC inhibitors with AR antagonist in CaP therapy. Trial completion date: Nov 2020 --> Nov 2021 | Trial primary completion date: Nov 2020 --> Nov 2021
- |||||||||| Zolinza (vorinostat) / Merck (MSD), Farydak (panobinostat) / Novartis, entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax Pharma
Review, Journal, IO Biomarker: Histone Deacetylase Inhibition in Non-small Cell Lung Cancer: Hype or Hope? (Pubmed Central) - Nov 11, 2020
In this paper, we review the available preclinical and clinical evidence for the use of HDACi in NSCLC. We also review the challenges precluding widespread clinical utility of HDACi as a cancer therapy and future directions.
- |||||||||| Leustatin (cladribine) / J&J
[VIRTUAL] Novel Combination Drug Regimens Using Hypomethylating Agents in Treatment of Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia () - Nov 5, 2020 - Abstract #ASH2020ASH_4981;
In addition, three studies compared outcomes of CDR involving decitabine with all trans retinoic acid (ATRA)(n=93, ORR=21.9% vs 13.5%, p=0.06; mOS= 8.2 m vs 5.1 m, p=0.006) or talacotuzumab (CR/CRi= 15% vs 11%, p=0.44; mOS= 5.36 m vs 7.26 m, p=0.78) or bortezomib (CR/CRi= 39% vs 38%, p=0.91, mOS=9.3 m vs 8.9,p=0.18) to decitabine alone...Drugs included midostaurin (n= 88 , CR/CRi=25-29% mOS= 6-8 m) and pracinostat (n= 50, CR/CRi =46% mOS=19.1 m), In addition, two studies compared outcomes using CDR involving AZA with panobinostat (n=22, CR= 22.4 vs 30.8%, OS at 1 year = 60% vs 70%) or entinostat (n=18, ORR= 0% vs 16.6%, mOS=6 m vs 13 m) to AZA alone...The above listed efficacious CDR involving decitabine in phase I/II studies need to be evaluated in large, randomized trials to assess for definitive benefit. If proven efficacious in larger studies, they could serve as additional first line CDR options in addition to HMA and venetoclax in treating elderly patients with newly diagnosed AML.
- |||||||||| bortezomib / Generic mfg.
Journal: Discovery of Peptide Boronate Derivatives as Histone Deacetylase (HDAC) and Proteasome Dual Inhibitors for Overcoming Bortezomib Resistance of Multiple Myeloma. (Pubmed Central) - Nov 3, 2020
The most potent inhibitors, ZY-2 and ZY-13 showed excellent inhibition against proteasome and good selectivity against HDACs. In particular, ZY-2 not only exhibited good antiproliferative activities on MM cell lines RPMI-8226, U266 and KM3 (IC50 values of 6.66 nM, 4.31 nM and 10.1 nM, respectively) but also showed more potent antiproliferative activities against the bortezomib resistant MM cell line KM3/BTZ compared with bortezomib (IC50 values of 8.98 nM vs. 226 nM, P < 0.01) and even better than the combination of HDAC inhibitor MS-275 and bortezomib (1:1) (IC50 values of 8.98 nM vs. 98.0 nM, P < 0.01).
- |||||||||| Zolinza (vorinostat) / Merck (MSD), entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax Pharma
[VIRTUAL] Class specific HDAC inhibition differentially affects the function of specific T cell subsets (virtual poster hall) - Nov 3, 2020 - Abstract #SITC2020SITC_2060;
Ongoing studies are aimed at elucidating the specific HDACs responsible for regulating T cell effector functions and tumor immunogenicity when targeted. Ultimately, understanding this could help identify inhibitors with the desired specificity profile for combining with immunotherapy.
- |||||||||| Zolinza (vorinostat) / Merck (MSD), entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax Pharma
[VIRTUAL] Class specific HDAC inhibition differentially affects the function of specific T cell subsets (virtual poster hall) - Nov 3, 2020 - Abstract #SITC2020SITC_1981;
Ongoing studies are aimed at elucidating the specific HDACs responsible for regulating T cell effector functions and tumor immunogenicity when targeted. Ultimately, understanding this could help identify inhibitors with the desired specificity profile for combining with immunotherapy.
- |||||||||| entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax Pharma
Journal: Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity. (Pubmed Central) - Oct 31, 2020
Induction was initially defined with respect to dose and time and compared with the APD Entinostat (MS-275)...The APD effects are mediated through Signal transducer and activator of transcription 3 (STAT3) activation. Utilization of induced innate immunity to fight infections can reduce antibiotic usage, might be effective against multidrug resistant bacteria and is in line with improved stewardship in healthcare.
- |||||||||| molibresib (GSK525762) / GSK, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Trial completion date, Trial primary completion date, Metastases: Testing a New Anti-cancer Drug Combination, Entinostat and GSK525762C, for Advanced and Refractory Solid Tumors and Lymphomas (clinicaltrials.gov) - Sep 28, 2020
P1, N=0, Withdrawn,
Pharmacodynamic analysis confirmed target inhibition in entinostat-treated patients. Trial completion date: Apr 2021 --> Sep 2020 | Trial primary completion date: Apr 2021 --> Sep 2020
- |||||||||| entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax
Preclinical, Journal: Regulatory mechanism of MS275 on the p38 MAPK signaling pathway in rats with convulsion in the developmental stage (Pubmed Central) - Sep 27, 2020
Trial completion date: Apr 2021 --> Sep 2020 | Trial primary completion date: Apr 2021 --> Sep 2020 In rats with convulsion in the developmental stage, the histone deacetylase inhibitor MS275 can inhibit the p38 MAPK signaling pathway, the apoptosis of hippocampal neurons, and the activation of microglial cells and thus reduce inflammatory response and convulsion-induced brain injury in a dose-dependent manner.
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