^
    4d
    Tinostamustine (EDO-S101), an Alkylating Deacetylase Inhibitor, Enhances the Efficacy of Daratumumab in Multiple Myeloma by Upregulation of CD38 and NKG2D Ligands. (PubMed, Int J Mol Sci)
    In vivo data confirmed that tinostamustine pretreatment followed by daratumumab administration significantly delayed tumor growth and improved the survival of mice compared to individual treatments. In summary, our results suggest that tinostamustine could be a potential candidate to improve the efficacy of anti-CD38 mAbs.
    Journal • IO biomarker
    |
    MICA (MHC Class I Polypeptide-Related Sequence A) • MICB (MHC Class I Polypeptide-Related Sequence B) • NKG2D (killer cell lectin like receptor K1)
    |
    CD38 expression
    |
    Darzalex (daratumumab) • tinostamustine (EDO-S101)
    4ms
    Study of Tinostamustine for Adjuvant Treatment of Glioblastoma (clinicaltrials.gov)
    P1, N=12, Active, not recruiting, Mundipharma Research Limited | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2023 --> Jul 2024
    Enrollment closed • Trial primary completion date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    tinostamustine (EDO-S101)
    8ms
    Study of Tinostamustine for Adjuvant Treatment of Glioblastoma (clinicaltrials.gov)
    P1, N=12, Recruiting, Mundipharma Research Limited | Trial completion date: Jul 2024 --> Nov 2024 | Trial primary completion date: Jul 2023 --> Nov 2023
    Trial completion date • Trial primary completion date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    tinostamustine (EDO-S101)
    10ms
    Open-label non-randomized phase IB study to characterize the safety, tolerability and recommended dose of tinostamustin in combination with nivolumab in patients with advanced melanoma (ENIGMA) (ESMO 2023)
    No severe myelosuppression was observed except a single case of grade 3 leucocytopenia.Ex vivo T-cell stimulation and ELISA from blood samples revealed induction of adaptive T-cell and antibody responses against tumor-associated antigens. Conclusions Tinostamustine at an immune-modulatory dose of 30 mg/m2 over 60 min is safe when co-administered with nivolumab 3mg/kg and resulted in 47% disease stabilization and 20% objective radiological responses in pts with advanced melanoma failing standard ICI treatment.
    Clinical • P1 data • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    Opdivo (nivolumab) • tinostamustine (EDO-S101)
    1year
    NCI-2018-00872: Tinostamustine With or Without Radiation Therapy in Treating Patients With Newly Diagnosed MGMT-Unmethylated Glioblastoma (clinicaltrials.gov)
    P1, N=92, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2022 --> Dec 2024 | Trial primary completion date: Oct 2022 --> Dec 2024
    Trial completion date • Trial primary completion date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    tinostamustine (EDO-S101)
    over1year
    Study of Tinostamustine for Adjuvant Treatment of Glioblastoma (clinicaltrials.gov)
    P1, N=12, Recruiting, Mundipharma Research Limited | Trial completion date: Jan 2024 --> Jul 2024
    Trial completion date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    tinostamustine (EDO-S101)
    almost2years
    Study of Tinostamustine for Adjuvant Treatment of Glioblastoma (clinicaltrials.gov)
    P1, N=12, Recruiting, Mundipharma Research Limited | Not yet recruiting --> Recruiting
    Enrollment open
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    tinostamustine (EDO-S101)
    almost2years
    Study of Tinostamustine for Adjuvant Treatment of Glioblastoma (clinicaltrials.gov)
    P1, N=12, Not yet recruiting, Mundipharma Research Limited
    New P1 trial
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    tinostamustine (EDO-S101)
    almost2years
    Tinostamustine With or Without Radiation Therapy in Treating Patients With Newly Diagnosed MGMT-Unmethylated Glioblastoma (clinicaltrials.gov)
    P1, N=92, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Oct 2021 --> Oct 2022 | Trial primary completion date: Oct 2021 --> Oct 2022
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    tinostamustine (EDO-S101)
    2years
    TINOSTAMUSTINE (EDO-S101), AN ALKYLATOR AND HISTONE DEACETYLASE INHIBITOR, ENHANCES THE EFFICACY OF DARATUMUMAB IN PRECLINICAL MODELS OF MULTIPLE MYELOMA (EHA 2022)
    It has shown anti-myeloma (MM) activity in different preclinical models both in monotherapy and in combination with bortezomib. Similar results were obtained in the NSG model. Conclusion Our preclinical data demonstrate that tinostamustine increases the anti-myeloma effect of daratumumab presumably due to enhanced expression of CD38 and MICA.
    Preclinical • IO biomarker • Epigenetic controller
    |
    CD38 (CD38 Molecule) • MICA (MHC Class I Polypeptide-Related Sequence A) • ANXA5 (Annexin A5) • MICB (MHC Class I Polypeptide-Related Sequence B) • NKG2D (killer cell lectin like receptor K1)
    |
    CD38 expression
    |
    bortezomib • Darzalex (daratumumab) • tinostamustine (EDO-S101)
    over3years
    Autophagy Inhibition Potentiates the Anticancer Effects of a Bendamustine Derivative NL-101 in Acute T Lymphocytic Leukemia. (PubMed, Biomed Res Int)
    Here, we report the antitumor potency of NL-101, a compound that combines the nitrogen mustard group of bendamustine with the hydroxamic acid group of vorinostat. Furthermore, inhibition of autophagy by 3-methyladenine increased apoptotic cell death by NL-101, suggesting a prosurvival role of autophagy. In summary, our finding provides rationale for investigation of NL-101 as a DNA/HDAC dual targeting drug in T-ALL, either as a single agent or in combination with autophagy inhibitors.
    Journal • PARP Biomarker
    |
    CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK2 (Cyclin-dependent kinase 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    CCNE1 expression • CDK2 expression
    |
    Zolinza (vorinostat) • bendamustine • tinostamustine (EDO-S101)