tinostamustine (EDO-S101) / Mundipharma, Purdue - LARVOL DELTA

Study of Tinostamustine for Adjuvant Treatment of Glioblastoma (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Mundipharma Research Limited | Active, not recruiting ➔ Completed

Trial completion • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT

A phase 1 study of tinostamustine, a novel alkylating deacetylase inhibitor, as adjuvant treatment in newly diagnosed MGMT promoter-unmethylated (uMGMT) glioblastoma (GBM) (SNO 2025) - P1 | "Background: Treatment with temozolomide (TMZ) offers limited benefit in patients with uMGMT GBM. Tinostamustine following RT/TMZ was associated with manageable toxicities in newly diagnosed uMGMT GBM patients at a MTD of 100 mg/m2 with encouraging efficacy signals. A planned future trial will further evaluate the RP2D of tinostamustine and impact on survival outcomes."

Clinical • P1 data • Brain Cancer • Glioblastoma • Hematological Disorders • Solid Tumor • Thrombocytopenia • MGMT

Results from the Cohort-Expansion Stage of a Phase I Trial of Tinostamustine Monotherapy in Advanced Hodgkin Lymphoma (HL), Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM) (NCT02576496) (ASH 2023) - P1 | "The principal TEAEs were haematological and gastrointestinal. An ORR of 30.4% and a median progression-free survival of 4.3 months were observed, revealing signals of efficacy in this heavily pre-treated patient population for whom no other standard therapy with proven clinical benefit was available or recommended."

Metastases • Monotherapy • P1 data • Anemia • Cutaneous T-cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Prolymphocytic Leukemia • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia

Results from the Cohort Expansion Stage of a Phase I Trial of Tinostamustine Monotherapy in Advanced Haematological Malignancies (NCT02576496): Findings from a Subset of Patients with Cutaneous T-Cell Lymphoma (CTCL) (ASH 2023) - P1 | "Tinostamustine was well tolerated, with no unexpected AEs. The principal TEAEs were haematological and gastrointestinal."

Clinical • Metastases • Monotherapy • P1 data • Acute Coronary Syndrome • Anemia • Cardiovascular • Cutaneous T-cell Lymphoma • Dermatology • Hematological Disorders • Hematological Malignancies • Interstitial Lung Disease • Leukopenia • Lymphoma • Mycosis Fungoides • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pulmonary Disease • Respiratory Diseases • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia

A phase 1 study of tinostamustine, a novel alkylating deacetylase inhibitor, as adjuvant treatment in newly diagnosed MGMT promoter-unmethylated (uMGMT) glioblastoma (GBM) (WFNOS 2025) - P1 | "Background: Treatment with temozolomide (TMZ) offers limited benefit in patients with uMGMT GBM. Tinostamustine following RT/TMZ was associated with manageable toxicities in newly diagnosed uMGMT GBM patients at a MTD of 100 mg/m2 with encouraging efficacy signals. A planned future trial will further evaluate the RP2D of tinostamustine and impact on survival outcomes."

Clinical • P1 data • Brain Cancer • Glioblastoma • Glioma • Hematological Disorders • Solid Tumor • Thrombocytopenia • MGMT

Tinostamustine Shows Early Signals of Activity in Phase 1 Glioblastoma Trial (Businesswire) - "Ten patients were enrolled, nine of whom were evaluable for safety and efficacy. The median patient age was 63 years, and most were male. Three patients received tinostamustine at 80 mg/m² without experiencing dose-limiting toxicities (DLTs). Among the six patients treated at 100 mg/m², one experienced a DLT of prolonged low-grade thrombocytopenia....The results will be shared as a poster at the 2025 Neuro-Oncology Societies Meeting on November 22 in Honolulu, Hawaii. The results were also presented in October at the 2025 European Association for Neuro-Oncology (EANO) meeting."

P1 data • Glioblastoma

FDA Grants Orphan Drug Designation for Tinostamustine in Malignant Glioma (Purdue Press Release)

Orphan drug • Glioma

A phase 1 study of tinostamustine, a novel alkylating deacetylase inhibitor, as adjuvant treatment in newly diagnosed MGMT promoter-unmethylated glioblastoma (EANO 2025) - P1 | "Background: Treatment with temozolomide (TMZ) offers limited benefit in patients with MGMT promoter-unmethylated (uMGMT) glioblastoma (GBM). Tinostamustine following RT/TMZ was associated with manageable toxicities in newly diagnosed uMGMT GBM patients at a MTD of 100 mg/m2 with encouraging efficacy signals. A planned future trial will further evaluate the RP2D of tinostamustine and impact on survival outcomes."

Clinical • P1 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT

Purdue Pharma…has entered into an agreement to have its pipeline medication tinostamustine included in the Phase 2/3 GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment) adaptive clinical trial for glioblastoma… (Businesswire) - "The study is anticipated to begin following IND submission and FDA approval of the protocol with activation in Canada, Europe, and Australia to follow."

Trial status • Glioblastoma

Imbrium Therapeutics to Showcase Pipeline Assets Open for Partnership at the BIO International Convention 2025 (Businesswire) - "Imbrium Therapeutics L.P...presenting pipeline developments at the BIO International Convention on Wednesday, June 18, at 9:15 a.m. in Room 153B. Imbrium is actively seeking partnerships to advance the development of investigational therapeutics for multiple indications across several disease areas including genitourinary disorders, substance use disorders, and cancerous malignancies. Imbrium is discussing two investigational agents...tinostamustine, both of which could present substantial revenue opportunities."

Clinical • Glioblastoma

Open-label nonrandomized phase IB study to characterize the safety and recommended dose of tinostamustine in combination with nivolumab in patients with advanced melanoma (ENIgMA). (PubMed, Melanoma Res) - "Median progression-free survival was 8.3 weeks [95% confidence interval (CI): 2.4-15.4 weeks), median overall survival was 19.1 weeks (95% CI: 2.4-41 weeks). Two-weekly intravenous tinostamustine at an immune-modulatory dose of 30 mg/m2 is safe when coadministered with nivolumab 3 mg/kg and resulted in 54% disease stabilization and 23% confirmed partial responses in patients with predominantly ICI-resistant, advanced melanoma."

Journal • P1 data • Hematological Disorders • Leukopenia • Melanoma • Oncology • Pneumonia • Solid Tumor • Thrombocytopenia

Tinostamustine (EDO-S101) and Its Combination with Celecoxib or Temozolomide as a Therapeutic Option for Adult-Type Diffuse Gliomas. (PubMed, Int J Mol Sci) - "Astrocytoma cells were more susceptible to the tested treatments than glioblastoma cells, and, generally, those dual therapies were superior in anti-glioma efficacy compared to temozolomide. Overall, our study provides evidence that tinostamustine and the combination therapies consisting of tinostamustine and celecoxib or tinostamustine and temozolomide may represent a new approach for the effective treatment of malignant gliomas."

Journal • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Malignant Glioma • Oncology • Solid Tumor

Safety and Efficacy of Tinostamustine in a Subpopulation of Patients With Relapsed/Refractory Hodgkin Lymphoma From a Phase I Trial. (PubMed, Hematol Oncol) - P1 | "This study demonstrates a predictable and manageable safety profile with signals of efficacy. Trial Registration: ClinicalTrials.gov identifier: NCT02576496."

Journal • P1 data • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Solid Tumor

Study of Tinostamustine, First-in-Class Alkylating HDACi Fusion Molecule, in Relapsed/Refractory Hematologic Malignancies (clinicaltrials.gov) - P1 | N=106 | Completed | Sponsor: Mundipharma Research Limited | Active, not recruiting ➔ Completed

Epigenetic controller • Trial completion • Cutaneous T-cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

NCI-2018-00872: Tinostamustine With or Without Radiation Therapy in Treating Patients With Newly Diagnosed MGMT-Unmethylated Glioblastoma (clinicaltrials.gov) - P1 | N=5 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed | N=92 ➔ 5 | Trial completion date: Dec 2024 ➔ Jun 2024 | Trial primary completion date: Dec 2024 ➔ Jun 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor • MGMT

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."

IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • MICA • MICB • NKG2D

Study of Tinostamustine for Adjuvant Treatment of Glioblastoma (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Mundipharma Research Limited | Recruiting ➔ Active, not recruiting | Trial primary completion date: Nov 2023 ➔ Jul 2024

Enrollment closed • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

Hydroxamic acid hybrids: Histone deacetylase inhibitors with anticancer therapeutic potency. (PubMed, Eur J Med Chem) - "Notably, hydroxamic acid hybrids, exemplified by fimepinostat and tinostamustine as potential HDACis, could exert the anticancer effects through induction of apoptosis, differentiation, and growth arrest in cancer cells, representing useful scaffolds for the discovery of novel HDACis. The purpose of this review is to summarize the current scenario of hydroxamic acid hybrids as HDACis with anticancer therapeutic potential developed since 2020 to facilitate further rational exploitation of more effective candidates."

Epigenetic controller • Journal • Review • Oncology

Results from a phase I/II trial of tinostamustine monotherapy in advanced solid tumours (NCT03345485): Safety and efficacy in a subset of patients (pts) with soft tissue sarcoma (STS) (ESMO 2023) - P1/2 | "One pt with STS achieved PR as best response, and 3 had SD ≥4 mo duration; 5 pts with STS discontinued treatment due to progressive disease. Table: 1957P Demographic & safety data: Pts with advanced solid tumours receiving tinostamustine & the STS pt subset Conclusions Tinostamustine demonstrated modest signals of efficacy with manageable tolerability in pts with STS."

Clinical • Metastases • Monotherapy • P1/2 data • Oncology • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

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) - P1 | "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 • Combination therapy • Metastases • P1 data • Melanoma • Oncology • Solid Tumor • BRAF

Results From A Phase I/II Trial Of Tinostamustine Monotherapy In Advanced Solid Tumours (NCT03345485): Safety And Efficacy In A Subset Of Patients With Advanced Ovarian Cancer (OvCa) (ESGO 2023) - P1/2 | "1/18 patients with OvCa achieved a CR as best response, 1/18 PR, and 7/18 SD â¥4 monthsâ duration. 10/18 patients discontinued treatment due to progressive disease.Conclusion Tinostamustine demonstrated signals of efficacy with manageable tolerability in patients with OvCa."

Clinical • Metastases • Monotherapy • P1/2 data • Oncology • Ovarian Cancer • Solid Tumor

Study of the Safety, Pharmacokinetics and Efficacy of EDO-S101, in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=71 | Completed | Sponsor: Mundipharma Research Limited | Active, not recruiting ➔ Completed | N=167 ➔ 71

Enrollment change • Epigenetic controller • Metastases • Trial completion • Breast Cancer • Endometrial Cancer • Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Small Cell Lung Cancer • Soft Tissue Sarcoma • Solid Tumor • Triple Negative Breast Cancer

Study of Tinostamustine, First-in-Class Alkylating HDACi Fusion Molecule, in Relapsed/Refractory Hematologic Malignancies (clinicaltrials.gov) - P1 | N=106 | Active, not recruiting | Sponsor: Mundipharma Research Limited | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2023 ➔ Dec 2023 | Trial primary completion date: May 2023 ➔ Nov 2023

Enrollment closed • Epigenetic controller • Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

Study of Tinostamustine for Adjuvant Treatment of Glioblastoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: 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 • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

A phase II study of tinostamustine in patients (pts) with advanced solid tumours. (ASCO 2023) - P1/2 | "Tinostamustine demonstrated modest signals of efficacy, with 2 pts achieving a PR, and manageable tolerability in pts with advanced solid tumours for whom no other standard therapy with proven clinical benefit was available or recommended. Further studies are needed to fully explore the benefits of tinostamustine in solid tumours. Clinical trial information: NCT03345485."

Clinical • Metastases • P2 data • Endometrial Cancer • Hematological Disorders • Lung Cancer • Neuroendocrine Tumor • Oncology • Pulmonary Disease • Sarcoma • Small Cell Lung Cancer • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • Triple Negative Breast Cancer