navtemadlin (KRT-232) / Kartos Therap 
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 7 Diseases   15 Trials   15 Trials   324 News 


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  • ||||||||||  Nutlin-3 / EMD Serono, navtemadlin (KRT-232) / Kartos Therap
    MDM2 inhibition as a novel radio-sensitizing strategy for endometrial cancer (Section 44; Poster Board #4) -  Mar 14, 2023 - Abstract #AACR2023AACR_2327;    
    Overall, these findings nominate MDM2 inhibitors as potential radio-sensitizing strategies that would be applicable to a large proportion of EC. Given the lack of benefit from cisplatin-based radio-sensitization for recurrent EC in a recent clinical trial, this provides a novel biomarker driven strategy.
  • ||||||||||  Legalon (silibinin) / Mylan, navtemadlin (KRT-232) / Kartos Therap, ralimetinib (LY 2228820) / Eli Lilly
    Review, Journal:  Anticancer Mechanism of Flavonoids on High-Grade Adult-Type Diffuse Gliomas. (Pubmed Central) -  Mar 2, 2023   
    Moreover, the clinical relevance of flavonoid molecular targets in high-grade adult-type diffuse gliomas is discussed with comparison to small molecules inhibitors: ralimetinib, AMG232, marimastat, hydroxychloroquine and chloroquine. Despite the positive pre-clinical results, further investigations in clinical studies are warranted to substantiate the efficacy and safety of the use of flavonoids on high-grade adult-type diffuse glioma patients.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, navtemadlin (KRT-232) / Kartos Therap
    Trial completion date, Trial primary completion date, Combination therapy:  Testing a New Chemotherapy Drug, KRT-232 (AMG-232) in Combination With Decitabine and Venetoclax in Patients With Acute Myeloid Leukemia (clinicaltrials.gov) -  Feb 21, 2023   
    P1b,  N=48, Suspended, 
    Despite the positive pre-clinical results, further investigations in clinical studies are warranted to substantiate the efficacy and safety of the use of flavonoids on high-grade adult-type diffuse glioma patients. Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
  • ||||||||||  M7583 / EMD Serono, Telios Pharma
    Enrollment closed, Enrollment change:  TL-895 and KRT-232 Study in Acute Myeloid Leukemia (clinicaltrials.gov) -  Feb 17, 2023   
    P1b/2,  N=18, Active, not recruiting, 
    Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023 Recruiting --> Active, not recruiting | N=70 --> 18
  • ||||||||||  navtemadlin (KRT-232) / Kartos Therap
    Journal:  AMG232 inhibits the angiogenesis in glioma through p53/RBM4/VEGFR2 pathway. (Pubmed Central) -  Jan 6, 2023   
    Finally, AGM232 resulted in a significant decrease in new vessels and hemoglobin content in vivo. This study proved AMG232 inhibited glioma angiogenesis by blocking the MDM2-p53 interaction, in which the p53/RBM4/VEGFR2 pathway played an important role.
  • ||||||||||  navtemadlin (KRT-232) / Kartos Therap
    Trial completion date, Trial primary completion date:  NRG-DT001: Navtemadlin and Radiation Therapy in Treating Patients With Soft Tissue Sarcoma (clinicaltrials.gov) -  Jan 4, 2023   
    P1,  N=46, Active, not recruiting, 
    This study proved AMG232 inhibited glioma angiogenesis by blocking the MDM2-p53 interaction, in which the p53/RBM4/VEGFR2 pathway played an important role. Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
  • ||||||||||  navtemadlin (KRT-232) / Kartos Therap
    Trial completion date, Trial primary completion date, Combination therapy:  Testing the Addition of KRT-232 (AMG 232) to Usual Chemotherapy for Relapsed Multiple Myeloma (clinicaltrials.gov) -  Jan 4, 2023   
    P1,  N=40, Recruiting, 
    Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023 Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
  • ||||||||||  navtemadlin (KRT-232) / Kartos Therap
    P3 data, Review, Journal, IO biomarker:  BOREAS: a global, phase III study of the MDM2 inhibitor navtemadlin (KRT-232) in relapsed/refractory myelofibrosis. (Pubmed Central) -  Nov 24, 2022   
    Navtemadlin demonstrated promising clinical and disease-modifying activity and acceptable safety in a phase II study in patients with relapsed/refractory MF. The randomized phase III BOREAS study compares the efficacy and safety of navtemadlin to best available therapy in patients with MF that is relapsed/refractory to JAK inhibitor treatment.
  • ||||||||||  Characterize Biomarkers and Mechanisms of Resistance for MDM2 Inhibitors in AML (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_5757;    
    Finally, we observed that combining a FLT3/IRAK dual inhibitor, pacritinib, or an IRAK1 /IL-1 receptor antagonist, anakinra, partially rescued IL-1a and IL-1ß mediated drug resistance of MDM2 inhibitors. As such, we uncovered the role of leukemia-associated monocyte in driving intrinsic and extrinsic MDM2 inhibitor resistance and the potential underlying mechanisms.
  • ||||||||||  Deep Multi-Omics Profiling in Cytogenetically Poor-Risk AML (ENMCC - Hall E) -  Nov 4, 2022 - Abstract #ASH2022ASH_3400;    
    For example, we validated TP53 WT status as a determinant of response to MDM2 inhibitors (AMG-232, idasanutlin, SAR405838 and NVP-CGM097) and we found that within the TP53-WT group of patients, good-responders have a significantly lower expression of TP53 pathway genes at diagnosis compared to non-responders. Altogether, these findings demonstrate the feasibility of simultaneously generating multi-omics data from several different platforms in AML primary samples and highlights that integrative analysis will increase our understanding of the biology of the disease and its therapeutic vulnerabilities.
  • ||||||||||  navtemadlin (KRT-232) / Kartos Therap
    Optimizing MDM2 inhibition for the treatment of glioblastoma (West/Central Hall) -  Sep 28, 2022 - Abstract #SNO2022SNO_646;    
    We have analyzed clinical samples from 10 patients newly diagnosed with glioblastoma multiforme (GBM) and treated with the MDM2 inhibitor KRT-232...Cell death via apoptosis can be achieved when MDM2 inhibition is combined with the chemotherapeutic agent temozolomide...This suggests that other factors, in addition to p53 mutational status, mediate response to MDM2 inhibition in gliomas. Transcriptional analyses of patient samples following drug treatment suggest that cell division, chromatin reorganization, cell differentiation state and immune response programs become deregulated under MDM2 inhibition and in the absence of p53-inactivating mutations.
  • ||||||||||  Extended Abstract: Novel Therapies for PV () -  Sep 22, 2022 - Abstract #SOHO2022SOHO_371;    
    P2, P2a/2b
    Polycythemia vera, ropeginterferon, ruxolitinib, targeted agents, hepcidin Polycythemia vera (PV), the most common classical Philadelphia chromosome negative myeloproliferative neoplasm (MPN), is defi ned by hyperproliferative marrow resulting in erythrocytosis, certain degree of marrow fi brosis, systemic symptoms and splenomegaly...Hydroxyurea (HU) has been the most commonly used frontline cytoreductive therapy...While longer follow-up and larger data are needed to determine whether the observed molecular response could translate into improved long-term outcomes of PV patients, preliminary report from a single center that used interferon for almost 4 decades suggested its benefi t for overall survival and disease transformation.7 While the approval of ropeginterferon alfa-2b has no specifi c designation for frontline vs subsequent use, we envision that this agent will dominate therapies of younger individuals seeking deeper disease control and treatment free remissions...Targeting DNA transcription by inhibiting histone deacetylation is an intriguing area across numerous malignancies, including PV, where HDAC inhibitors also demonstrated ability to decrease JAK2 V617F protein levels, growth of JAK2 mutated cells and inhibit downstream JAK2 signaling.11 Although development of HDAC-i vorinostat in PV was stopped due to high rate of nonhematologic adverse events, novel HDAC-i givinostat showed more promising tolerance...MDM2 overexpression, reported in patients with PV, downregulates TP53 activity and its apoptotic effects on MPN cells.16 Despite the favorable control of hematocrit showed in 50% of patients with HU refractory/resistant PV treated with oral MDM2 antagonist, idasanutlin, in phase 1 and 2 clinical trials, further development of this agent was halted due to its poor tolerability (gastrointestinal toxicity).17,18 Novel and more potent MDM2 inhibitor, KRT-232, has currently ongoing phase 2 trial for patients with PV resistant/intolerant to HU (NCT03669965), and preliminary results are awaiting...Interim data on 62 patients showed that the agent reverses iron defi ciency and leads to phlebotomy independence in virtually all treated patients, improves MPN symptoms in majority of them and is well-tolerated.21 Double blind, phase 3 study, planning to randomize 250 PV patients on ongoing therapy to additional PTG-300 or placebo is about to be initiated...Few novel agents exploiting mechanisms critical to MPN proliferation and evolution hold promise in their clinical developments. The impact of these agents on patient’s overall survival remains to be determined.
  • ||||||||||  M7583 / EMD Serono, Telios Pharma
    Trial completion date, Trial primary completion date:  TL-895 and KRT-232 Study in Acute Myeloid Leukemia (clinicaltrials.gov) -  Aug 8, 2022   
    P1b/2,  N=70, Recruiting, 
    Trial completion date: Feb 2024 --> Dec 2024 Trial completion date: Jun 2024 --> Nov 2025 | Trial primary completion date: Jun 2022 --> Nov 2024
  • ||||||||||  Review, Journal:  The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes. (Pubmed Central) -  Jun 24, 2022   
    To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.
  • ||||||||||  navtemadlin (KRT-232) / Kartos Therap
    Enrollment open:  KRT-232 in Subjects With Relapsed or Refractory Small Cell Lung Cancer (clinicaltrials.gov) -  Apr 14, 2022   
    P2,  N=38, Recruiting, 
    Incorporating NGS sequencing results as an integral biomarker in a clinical trial of neoadjuvant radiotherapy and a radiosensitizer is feasible. Not yet recruiting --> Recruiting
  • ||||||||||  idasanutlin (RO5503781) / Roche, navtemadlin (KRT-232) / Kartos Therap
    Preclinical, Journal:  Epstein Barr virus-positive B-cell lymphoma is highly vulnerable to MDM2 inhibitors in vivo. (Pubmed Central) -  Apr 12, 2022   
    Moreover, treatment with navtemadlin resulted in tumor regression and prevented systemic dissemination of EBV+ lymphoma derived from 2 juvenile patients with posttransplant lymphoproliferative diseases, including one whose tumor was resistant to virus-specific T-cell therapy. These results provide proof-of-concept for targeted therapy of EBV+ lymphoma with MDM2i and the feasibility of using EBV infection or loss of BCL6 expression to identify responders to MDM2i.