numidargistat (INCB001158) / Calithera 
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 0 Diseases   3 Trials   3 Trials   64 News 


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  • ||||||||||  numidargistat (INCB001158) / Calithera
    Journal:  Establishing Gene Expression and Knockout Methods in Esteya vermicola CBS115803. (Pubmed Central) -  Oct 13, 2024   
    Moreover, we successfully implemented a split-marker strategy to delete the EvIPMD gene in E. vermicola CBS115803. In summary, our findings present valuable experimental methodologies for gene function analysis in E. vermicola CBS115803.
  • ||||||||||  numidargistat (INCB001158) / Incyte
    Journal, PD(L)-1 Biomarker, IO biomarker:  Arginase 1 is a key driver of immune suppression in pancreatic cancer. (Pubmed Central) -  Jun 14, 2023   
    Treatment of established tumors with the arginase inhibitor CB-1158 exhibited further increased CD8 T cell infiltration, beyond that seen with the macrophage-specific knockout, and sensitized the tumors to anti-PD1 immune checkpoint blockade. Our data demonstrate that Arg1 drives immune suppression in pancreatic cancer by depleting Arginine and inhibiting T cell activation.
  • ||||||||||  numidargistat (INCB001158) / Incyte
    ARGININE DEPRIVATION INDUCES ACQUISITION OF A SENESCENT PHENOTYPE AND FAVORS GENOMIC INSTABILITY IN MULTIPLE MYELOMA PLASMA CELLS (Poster area) -  May 12, 2023 - Abstract #EHA2023EHA_1085;    
    Our previous work showed that in vivo the treatment with arginase inhibitor CB1158 could reduce MM growth while increasing serum arg concentrations without affecting the infiltrates of myeloid cells... Taken together, our findings suggest that arginine deprivation, while inducing immune dysfunction, conveys a complex adaptive response which causes a chromatin remodeling that leads to the acquisition of a senescencephenotype to select the most fit clone and favors genomic instability, providing new insights to improve immunotherapy and induce synthetic lethality in MM.
  • ||||||||||  numidargistat (INCB001158) / Incyte
    Biomarker, Journal, IO biomarker:  Surface TREM2 on circulating M-MDSCs as a novel prognostic factor for adults with treatment-na (Pubmed Central) -  Apr 8, 2023   
    Taken together, our findings suggest that arginine deprivation, while inducing immune dysfunction, conveys a complex adaptive response which causes a chromatin remodeling that leads to the acquisition of a senescencephenotype to select the most fit clone and favors genomic instability, providing new insights to improve immunotherapy and induce synthetic lethality in MM. In treatment-na
  • ||||||||||  numidargistat (INCB001158) / Incyte
    Inhibition of murine myeloid suppressor cells increases CD8+ T cell activation in Vitro (Section 17; Poster Board #16) -  Mar 14, 2023 - Abstract #AACR2023AACR_4932;    
    An ARG1 target is currently in clinical trials (INCB001158, CB-1158 from Calithera Biosciences) and was used as a target of interest in this study.MDSC generation from bone marrow cells (BM) was compared using GM-CSF and IL-6 or GM-CSF, IFN?, and LPS...Similar trends were observed with CD69, PD-1, IFN-y, TNF-a and IL-2 expression in CD8+ T cells. Overall, the ability to monitor changes in T cell activation following MDSC has broad applications in in vitro screening of novel drug compounds that alter the TME as well as sets the experimental framework for ex vivo analysis of cells isolated from TME following treatment.
  • ||||||||||  numidargistat (INCB001158) / Calithera
    Trial completion, Combination therapy, Metastases:  A Phase 1/2 Study of INCB001158 in Combination With Chemotherapy in Subjects With Solid Tumors (clinicaltrials.gov) -  Dec 23, 2022   
    P1/2,  N=149, Completed, 
    These results demonstrate the promise of using these classes of drugs to reduce treatment-related lymphopenia and immunosuppression. Active, not recruiting --> Completed
  • ||||||||||  numidargistat (INCB001158) / Incyte
    Preclinical, Journal:  Preclinical evidence of a direct pro-survival role of arginine deprivation in multiple myeloma. (Pubmed Central) -  Oct 1, 2022   
    Arginase inhibition significantly raised serum arginine concentration, reduced tumor growth by caliper assessment, and decreased intra-tumor AKT phosphorylation in vivo. Altogether, our results reveal a novel direct pro-survival effect of arginine deprivation on myeloma cells, with potential therapeutic implications.
  • ||||||||||  numidargistat (INCB001158) / Calithera
    Trial completion date, Trial primary completion date, Combination therapy, Metastases:  A Phase 1/2 Study of INCB001158 in Combination With Chemotherapy in Subjects With Solid Tumors (clinicaltrials.gov) -  Apr 13, 2022   
    P1/2,  N=149, Active, not recruiting, 
    Active, not recruiting --> Completed Trial completion date: Mar 2022 --> Jun 2022 | Trial primary completion date: Mar 2022 --> Jun 2022
  • ||||||||||  Zynyz (retifanlimab-dlwr) / Incyte, numidargistat (INCB001158) / Calithera
    Trial completion, Trial completion date, Trial primary completion date:  INCMGA 0012-104: A Study of INCMGA00012, INCB001158, and the Combination in Japanese Participants With Advanced Solid Tumors (clinicaltrials.gov) -  Feb 25, 2022   
    P1b,  N=18, Completed, 
    Terminated --> Active, not recruiting | Trial completion date: Jun 2021 --> Mar 2022 | Trial primary completion date: Jun 2021 --> Mar 2022 Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Dec 2021 | Trial primary completion date: Dec 2022 --> Dec 2021
  • ||||||||||  numidargistat (INCB001158) / Calithera
    Trial completion date, Trial primary completion date, Combination therapy, Metastases:  A Phase 1/2 Study of INCB001158 in Combination With Chemotherapy in Subjects With Solid Tumors (clinicaltrials.gov) -  Nov 12, 2021   
    P1/2,  N=149, Active, not recruiting, 
    Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Dec 2021 | Trial primary completion date: Dec 2022 --> Dec 2021 Trial completion date: Oct 2021 --> Mar 2022 | Trial primary completion date: Oct 2021 --> Mar 2022
  • ||||||||||  numidargistat (INCB001158) / Incyte
    Targeting M2-Tumor Associated Macrophages By Arginase-1 and PD-L1 in Regulating Juvenile Myelomonocytic Leukemia (JMML) Development and Relapse (GWCC - Hall B5, Level 1) -  Nov 5, 2021 - Abstract #ASH2021ASH_3043;    
    After 8 weeks post transplantation, we investigated the role of Arg-1 and PD-L1 in Shp2* recipients using pharmacological inhibitors, CB-1158 (Arg-1 inhibitor; 100 mg/kg, orally) + anti-PD-L1 antibody (10 mg/kg, i.p) for 30 days...These data suggest that the suppression of arginase-1 allows for the arginine levels to increase, which promotes the proliferation of T-cells. Increasing arginine levels also promotes an anti-tumor immune response resulting in the emergence of CD45.1 WT HSCs as opposed to mutant CD45.2 HSCs, suggesting that Arg-1 + PD-L1 treatment is a novel therapeutic approach to treat patients with JMML and for preventing leukemia relapse after BM transplantation.
  • ||||||||||  numidargistat (INCB001158) / Incyte
    Journal:  Cytokine-Mediated Regulation of ARG1 in Macrophages and Its Impact on the Control of Salmonella enterica Serovar Typhimurium Infection. (Pubmed Central) -  Oct 28, 2021   
    Furthermore, ARG1 was dispensable for pathogen control irrespective of the presence or absence of the phagolysosomal natural resistance-associated macrophage protein 1 (NRAMP1). Thus, unlike the detrimental function of ARG1 seen during infections with other intraphagosomal microorganisms, ARG1 did not support bacterial survival in systemic salmonellosis, indicating differential roles of arginine metabolism for host immune response and microbe persistence depending on the type of pathogen.
  • ||||||||||  numidargistat (INCB001158) / Calithera
    Trial completion date, Trial primary completion date, Combination therapy, Metastases:  A Phase 1/2 Study of INCB001158 in Combination With Chemotherapy in Subjects With Solid Tumors (clinicaltrials.gov) -  Apr 22, 2020   
    P1/2,  N=249, Recruiting, 
    Recruiting --> Active, not recruiting Trial completion date: May 2020 --> Oct 2021 | Trial primary completion date: Mar 2020 --> Oct 2021
  • ||||||||||  Avastin (bevacizumab) / Roche, paclitaxel / Generic Mfg.
    Drug-Induced Thrombocytopenia (Myelodysplastic Syndromes) -  Sep 26, 2019 - Abstract #SOHO2019SOHO_589;    
    P1/2
    Thereafter, patient was started on steroids with a marked improvement of the platelets count and currently she is on Paclitaxel monotherapy with a partial response as shown by the latest radiological and clinical evaluation.Conclusions Drug-induced immune thrombocytopenia can be triggered by a wide range of medications but in the current literature this the first case of DIITP related to INCB01158 (an oral inhibitor of arginase).1. https://clinicaltrials.gov/ct2/show/NCT03314935