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    DRUG:

    dencatistat (STP938)

    i
    Other names: STP938
    Associations

    News

    Trials
    Company:
    Step Pharma
    Drug class:
    CTPS1 inhibitor
    Associations

    News

    Trials
    8ms
    A Phase 1 Study to Assess STP938 as a Monotherapy in Adults With High Risk Essential Thrombocythaemia (clinicaltrials.gov)
    P1, N=20, Recruiting, Step Pharma, SAS | Not yet recruiting --> Recruiting
    Enrollment open
    |
    hydroxyurea • dencatistat (STP938)
    1year
    A Phase 1 Study to Assess STP938 as a Monotherapy in Adults With High Risk Essential Thrombocythaemia (clinicaltrials.gov)
    P1, N=20, Not yet recruiting, Step Pharma, SAS
    New P1 trial
    |
    hydroxyurea • dencatistat (STP938)
    over1year
    Study of STP938 in Advanced Solid Tumours (clinicaltrials.gov)
    P1, N=70, Recruiting, Step Pharma, SAS | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    dencatistat (STP938)
    almost2years
    A Phase 1 Study of STP938 for Adult Subjects With Advanced Solid Tumours (clinicaltrials.gov)
    P1, N=70, Not yet recruiting, Step Pharma, SAS
    New P1 trial • Metastases
    |
    dencatistat (STP938)
    over2years
    MYC-induced cytidine metabolism regulates survival and drug resistance via cGas-STING pathway in mantle cell lymphoma. (PubMed, Br J Haematol)
    Of these six genes, de novo CTP synthesis pathway enzyme CTPS1 whose inhibitor (STP938) is already in clinical trials for relapsed/refractory lymphomas (NCT05463263) has the highest regression coefficient. Additionally, MYC positively regulates CTPS1 expression, and TP53-aberrant and ibrutinib-resistant MCL cells also rely on cytidine metabolism. Furthermore, besides the obvious decreased CTP pool caused by CTPS1 deficiency, CTPS1 inhibition may also induce immune-related responses via activating dsDNA-cGAS-STING pathway, which plays a crucial role in impeding tumour growth in MCL patients.
    Journal
    |
    TP53 (Tumor protein P53) • CTPS1 (CTP Synthase 1)
    |
    TP53 expression • MYC positive
    |
    Imbruvica (ibrutinib) • dencatistat (STP938)
    almost3years
    A PHASE 1/2 STUDY OF STP938, A FIRST IN CLASS INHIBITOR OF CTP SYNTHASE 1, IN PATIENTS WITH RELAPSED/REFRACTORY B OR T CELL LYMPHOMA (ICML 2023)
    The phase 1 study (NCT05463263) opened to enrolment in the US and UK in September 2022. The phase 2 study will include additional centres in France.
    Clinical • P1/2 data
    |
    IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • CTPS1 (CTP Synthase 1) • CTPS2 (CTP Synthase 2)
    |
    dencatistat (STP938)
    almost3years
    A phase 1/2 study of STP938, a first-in-class inhibitor of CTP synthase 1, in patients with relapsed/refractory B or T cell lymphoma. (ASCO 2023)
    The phase 2 study will include additional centers in France. Clinical trial information: NCT05463263.
    Clinical • P1/2 data
    |
    IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • CTPS1 (CTP Synthase 1) • CTPS2 (CTP Synthase 2)
    |
    dencatistat (STP938)
    3years
    A Phase 1/2 Study of STP938, a First in Class Inhibitor of CTP Synthase 1, in Patients with Relapsed/Refractory B or T Cell Lymphoma (ASH 2022)
    Tumour genomics will be assessed by sequencing of circulating tumour DNA (ctDNA) prior to treatment and at disease progression using a bespoke genomic assay designed to elucidate biomarkers of response and understand mechanisms of resistance.Current statusThe study protocol has received FDA and MHRA approval. The phase 1 study (NCT05463263) will open to enrolment in the US and UK in August 2022.
    Clinical • P1/2 data
    |
    IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2)
    |
    dencatistat (STP938)
    over3years
    STP938, a Selective CTPS1 Inhibitor, Shows Single Agent Activity and Synergy with BCL2 Inhibition in Preclinical Models of Mantle Cell Lymphoma (ASH 2022)
    Of note, sensitivity to STP938 was independent of known indicators of poor prognosis, such as TP53 mutation, and was independent of resistance to standard of care therapies such as ibrutinib or venetoclax...Conclusions Dependence of tumor cells on elevated rates of nucleotide synthesis has been exploited by agents such as cytarabine...STP938, a highly selective CTPS1 inhibitor, demonstrates single agent activity in vitro and in vivo, and shows strong synergy with the approved BCL2 inhibitor venetoclax. STP938 will enter clinical development for relapsed refractory B and T cell lymphomas in 2022.
    Preclinical • IO biomarker
    |
    TP53 (Tumor protein P53) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1)
    |
    TP53 mutation • MCL1 expression
    |
    Venclexta (venetoclax) • Imbruvica (ibrutinib) • cytarabine • dencatistat (STP938)