Phase 1/2 Open-label Trial of Tinostamustine Conditioning and Autologous Stem Cell Transplantation for Salvage Treatment in Relapsed / Refractory Multiple Myeloma (TITANIUM 1)

Phase 1
The primary objectives of Phase 1 of this study are to:
Establish the safety, toxicity, and maximum tolerated dose (MTD) of the tinostamustine conditioning regimen.
Identify the recommended Phase 2 dose (RP2D) of tinostamustine for use in the Phase 2 portion of the study.
The secondary objective of Phase 1 of this study is to:
- Investigate the pharmacokinetics (PK) of tinostamustine.

Start Date15 Oct 2018

Sponsor / Collaborator

Mundipharma EDO GmbH

NCT04279938 / WithdrawnPhase 1IIT

A Phase Ib Combination Study of Rituximab, TinostamustinEAnd CHeckpoint Inhibition With Pembrolizumab in Relapsed/Refractory DLBCL - REACH

Safety run-in (part 1): Relapsed or refractory B-cell Non-Hodgkin lymphoma (NHL)
Main study (part 2): Relapsed or refractory diffuse large B-cell lymphoma

Start Date01 Sep 2018

Sponsor / Collaborator

Royal Marsden NHS Foundation Trust

[+2]

NCT02094560 / TerminatedPhase 2

Phase II Trial of CAP7.1 in Adult Patients With Refractory Malignancies: Small Cell Lung Carcinoma, Non-Small Cell Lung Carcinoma, Biliary Carcinoma (PIITCAP)

To assess the anti-tumor activity of CAP7.1 based on the observed objective response rate and rate of disease stabilization, as defined by the below primary and secondary endpoints, in patients with Non-Small Cell Lung Carcinoma (NSCLC), SCLC or biliary cancer who have progressed despite one or more previous chemotherapy line.

Start Date08 Nov 2011

Sponsor / Collaborator

CellAct Pharma GmbH

[+1]

100 Clinical Results associated with Mundipharma EDO GmbH

0 Patents (Medical) associated with Mundipharma EDO GmbH

Literatures (Medical) associated with Mundipharma EDO GmbH

01 Oct 2019·Annals of Oncology

Post-hoc analyses of a subgroup of patients with advanced biliary tract cancer (BTC) who crossed over to treatment with etoposide toniribate (EDO-S7.1) in a randomized phase II study

Author: U.-F. Pape ; S. Heeg ; O. Burkhard ; J. Meiler ; M. Sinn ; R. Arsenic ; A. Vogel ; K. Caca ; S. Kasper ; A.A. Kuhl ; I. Wagner ; N. Utku ; V. Rodriguez Laval ; T. Mehrling ; L. Mueller ; H. Jansen ; K. Hilgier

Abstract Background Etoposide toniribate (also known as EDO-S7.1, and previously known as CAP7.1), a novel topoisomerase II inhibitor, is activated in the presence of carboxylesterases. In specific tumor cell lines, it was found to be more active than etoposide, with in vivo activity demonstrated in several drug-resistant tumor models. Anti-tumor activity was confirmed in a Phase II randomized study in patients (pts) with relapsed BTC. Methods Pts with BTC and disease progression after ≥1 line of chemotherapy were randomized 1:1 to 3-week cycles of etoposide toniribate (200 or 150mg/m2; iv on days 1–5), or best supportive care (BSC). Pts who progressed on BSC crossed over to receive etoposide toniribate. Efficacy data collected after crossover were evaluated separately as part of this post-hoc exploratory analysis. Results The per protocol analysis set included 19 pts: 10 pts were randomized to BSC, and crossed over to etoposide toniribate after disease progression, 9 pts were randomized directly to the etoposide toniribate treatment arm. Treatment after crossover from BSC to etoposide toniribate was associated with a trend for improved disease control: n/N (%; 95% CI) 4/10 (40%; 12.2, 73.8) vs 2/10 (20%; 2.5, 55.6), with tumor control achieved in 4/10 patients (1 pt partial response, 3 pts stable disease). Risk of disease progression was 2.33 times higher during BSC treatment vs after crossover to etoposide toniribate. Crossover from BSC to etoposide toniribate was associated with a trend for prolonged median PFS (39 vs 50 days). Median OS for pooled etoposide toniribate and crossover pts was 145 (59, 243) days, estimated 1-year OS 14.1%. Median (95% CI) OS for etoposide toniribate vs crossover pts was 180 (43, 468) vs 83 (11, 243) days, HR 0.39 (0.13, 1.18), estimated 1-year OS 29.6% (5.2%, 60.7%) vs 0%. Conclusions This post-hoc analysis provides further evidence for the efficacy of etoposide toniribate and suggests that early initiation in pts with advanced BTC may offer a potential survival benefit. The efficacy of etoposide toniribate will be further investigated in a planned phase III study. Funding: CellAct Pharm GmbH and Mundipharma EDO GmbH. Clinical trial identification NCT02094560. Editorial acknowledgement Sarah Birch, PhD, at Makara Health Communications Ltd, UK, funded by Mundibiopharma Ltd. Legal entity responsible for the study CellAct Pharma GmbH. Funding CellAct Pharma GmbH, Mundipharma EDO GmbH. Disclosure U. Pape: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Shire; Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ipsen. S. Kasper: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD; Research grant / Funding (self): Celgene; Research grant / Funding (self), Travel / Accommodation / Expenses: Lilly. J. Meiler: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi/Aventis. M. Sinn: Honoraria (self): Amgen; Honoraria (self), Research grant / Funding (self): Leo Pharma; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Incyte; Research grant / Funding (self): Merck Sharp and Dohme; Research grant / Funding (self): Servier; Research grant / Funding (self): Taiho Pharmaceutical. H. Jansen: Advisory / Consultancy: CellAct Pharma. T. Mehrling: Leadership role, Full / Part-time employment: Mundipharma EDO. K. Hilgier: Advisory / Consultancy: Mundipharma EDO. I. Wagner: Full / Part-time employment: Mundipharma EDO. N. Utku: Honoraria (self), Advisory / Consultancy, Leadership role, Research grant / Funding (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: CellAct Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Mundipharma EDO; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

01 Jul 2019·Cancer Research

Abstract CT023: Dose escalation of tinostamustine in patients with advanced solid tumors

Author: Loeffler, Markus ; Rimmel, Bobbie J. ; Mehrling, Thomas ; Kummar, Shivaani ; Bui, Nam ; Natale, Ronald B. ; Mita, Alain

AbstractDespite advances in the treatment of solid tumors in recent years, unmet medical needs remain for patients with advanced disease. The alkylating deacetylase inhibiting molecule tinostamustine (EDO-S101) is a novel multi-action drug that has been shown in preclinical studies to improve drug access to the DNA strands within cancer cells, break them and counteract damage repair. Here we report findings from the dose escalation phase of an open-label Phase I/II study to investigate the safety, pharmacokinetics and efficacy of tinostamustine in patients with advanced solid tumors (NCT03345485).In the Phase I part of the study, patients were recruited using a standard 3+3 design, with the first cohort receiving 60mg/m2 tinostamustine administered IV over 30 minutes, with six ascending cohorts to a maximum dose of 100mg/m2 administered over 30 or 60 minutes.A total of 26 patients were screened and 22 patients enrolled into the study as the safety population. Patients had a mean ± SD age of 59.7 ± 11.1 years, 59.1% were female, 77.3% Caucasian and 22.7% Asian; all patients had received prior systemic therapy with or without radiotherapy. The (mean ± SD) tinostamustine dose was 407.3 ± 218.44 mg/m2, and the mean ± SD time on therapy was 10.4 ± 8.6 weeks. All patients experienced ≥1 treatment-emergent adverse events (TEAE), of which 22.7% were serious; 3 patients withdrew from the study due to TEAEs (CTCAE Grade 4 thrombocytopenia). The most common TEAEs related to study treatment were mild or moderate in intensity and included nausea (81.8% of patients), QTc prolongation (59.1%), thrombocytopenia (54.5%), anemia (45.5%), lymphopenia (40.9%), fatigue (36.4%), vomiting (31.8%) and leukopenia (31.8%). Importantly, despite a high percentage of patients experiencing some degree of QTc prolongation, external review determined that the majority of abnormalities were not clinically significant. Only one of the 22 patients enrolled (4.5%) experienced a QTc prolongation event that was considered to be clinically significant, this was a dose-limiting toxicity of Grade 3 QTc-prolongation in a patient receiving 100mg/m2 tinostamustine over 60 minutes. Nausea and vomiting were well managed using antiemetics. At 16 weeks’ follow-up, 4.5% of patients had a tumour response of partial response and 36.4% stable disease. Pharmacokinetic (PK) studies showed that peak serum concentrations (Cmax) of tinostamustine reached therapeutic levels. A more detailed analysis of PK data will be presented at the conference.In patients with advanced solid tumors and limited treatment options, tinostamustine was generally well tolerated with preliminary signs of efficacy observed in this Phase I study across diverse tumor types. The Phase II portion of this study will enable a more comprehensive assessment of the efficacy of tinostamustine in larger patient cohorts within five specific tumor types.Funding: Mundipharma-EDO GmbH.Citation Format: Alain Mita, Markus Loeffler, Nam Bui, Thomas Mehrling, Bobbie J. Rimmel, Ronald B. Natale, Shivaani Kummar. Dose escalation of tinostamustine in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT023.

01 Dec 2018·Journal of Hematology & OncologyQ1 · MEDICINE

The first-in-class alkylating deacetylase inhibitor molecule tinostamustine shows antitumor effects and is synergistic with radiotherapy in preclinical models of glioblastoma

Q1 · MEDICINE

ArticleOA

Author: Delle Monache, Simona ; Chen, Yi ; Pompili, Simona ; Cristiano, Loredana ; Colapietro, Alessandro ; Vetuschi, Antonella ; Marampon, Francesco ; Mehrling, Thomas ; Mancini, Andrea ; Tombolini, Vincenzo ; Gravina, Giovanni Luca ; Festuccia, Claudio ; Vitale, Flora

BACKGROUNDThe use of alkylating agents such as temozolomide in association with radiotherapy (RT) is the therapeutic standard of glioblastoma (GBM). This regimen modestly prolongs overall survival, also if, in light of the still dismal prognosis, further improvements are desperately needed, especially in the patients with O6-methylguanine-DNA-methyltransferase (MGMT) unmethylated tumors, in which the benefit of standard treatment is less. Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor (AK-DACi) molecule that fuses the DNA damaging effect of bendamustine with the fully functional pan-histone deacetylase (HDAC) inhibitor, vorinostat, in a completely new chemical entity.METHODSTinostamustine has been tested in models of GBM by using 13 GBM cell lines and seven patient-derived GBM proliferating/stem cell lines in vitro. U87MG and U251MG (MGMT negative), as well as T98G (MGMT positive), were subcutaneously injected in nude mice, whereas luciferase positive U251MG cells and patient-derived GBM stem cell line (CSCs-5) were evaluated the orthotopic intra-brain in vivo experiments.RESULTSWe demonstrated that tinostamustine possesses stronger antiproliferative and pro-apoptotic effects than those observed for vorinostat and bendamustine alone and similar to their combination and irrespective of MGMT expression. In addition, we observed a stronger radio-sensitization of single treatment and temozolomide used as control due to reduced expression and increased time of disappearance of γH2AX indicative of reduced signal and DNA repair. This was associated with higher caspase-3 activation and reduction of RT-mediated autophagy. In vivo, tinostamustine increased time-to-progression (TTP) and this was additive/synergistic to RT. Tinostamustine had significant therapeutic activity with suppression of tumor growth and prolongation of DFS (disease-free survival) and OS (overall survival) in orthotopic intra-brain models that was superior to bendamustine, RT and temozolomide and showing stronger radio sensitivity.CONCLUSIONSOur data suggest that tinostamustine deserves further investigation in patients with glioblastoma.

100 Deals associated with Mundipharma EDO GmbH

100 Translational Medicine associated with Mundipharma EDO GmbH

Corporation Tree

Boost your research with our corporation tree data.

view full example data

Pipeline

Pipeline Snapshot as of 16 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Other

Current Projects

Drug(Targets)	Indications	Global Highest Phase

Tinostamustine ( DNA x HDACs )	Relapse multiple myeloma More	Discontinued

Deal

Boost your decision using our deal data.

view full example data

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Profit

Explore the financial positions of over 360K organizations with Synapse.

view full example data

Grant & Funding(NIH)

Access more than 2 million grant and funding information to elevate your research journey.

view full example data

Investment

Gain insights on the latest company investments from start-ups to established corporations.

view full example data

Financing

Unearth financing trends to validate and advance investment opportunities.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Mundipharma EDO GmbH

Overview

Related

Corporation Tree

Pipeline

Pipeline Snapshot as of 16 Nov 2024

Current Projects

Deal

Translational Medicine

Profit

Grant & Funding(NIH)

Investment

Financing