Resminostat in combination with sorafenib in Asian patients with advanced hepatocellular carcinoma (HCC)

This study was a multi-national, multi-center, randomized, double-blind, placebo-controlled Phase II study to evaluate resminostat in combination with sorafenib for the first-line treatment of advanced HCC, conducted by our cooperation partner Yakult Honsha.

Recruitment status Completed
Study phase Phase II
Enrollment 170
Primary objective
  • Evaluate efficacy of the combination of resminostat and sorafenib versus sorafenib in the first-line treatment of advanced HCC patients
Secondary objectives
  • Safety
  • Quality of life (QOL)
  • Pharmacokinetic parameters
Exploratory objectives
  • Investigate the ability of plasma or serum biomarkers (e.g. vascular endothelial growth factor A, VEGF-A, or angiopoietin-2, Ang-2) and blood cellular mRNA biomarkers (e.g. zinc-finger protein 64 (Zfp64) mRNA) to predict subject prognosis and clinical efficacy of the treatments
  • Assess pharmacodynamics effects of resminostat and sorafenib
Poster Resminostat and sorafenib combination therapy for advanced hepatocellular carcinoma in patients previously untreated with systemic chemotherapy

Kudo M, Ryoo BY, Lim HY, Kim DY, Okusaka T, Ikeda M, Hidaka H, Yeon JE, Mizukoshi E, Morimoto M, Lee MA, Yasui K, Kawaguchi Y, Heo J, Morita S, Kim TY, Furuse J, Katayama K, Aramaki T, Tak WY.

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SHELTER – Combination of sorafenib and resminostat in hepatocellular carcinoma (HCC)

The SHELTER study was a multi-national, multi-center, single arm Phase II study to evaluate efficacy, safety and pharmacokinetics of resminostat and the treatment combination of sorafenib and resminostat in patients with HCC exhibiting progressive disease (PD) under sorafenib treatment.

Recruitment status Completed
Study phase Phase II
Enrollment 57
Primary objective
  • Evaluate efficacy of combination of resminostat and sorafenib versus standard treatment of sorafenib in second-line treatment of advanced HCC patients, investigating time to progression (TTP)
Secondary objectives
  • Overall survival (OS)
  • Progression free survival (PFS)
  • Overall response rate (ORR)
  • Duration of response (DOR)
  • Disease control rate (DCR)
  • Safety
  • Pharmacokinetics
Publication Resminostat plus sorafenib as second-line therapy of advanced hepatocellular carcinoma – The SHELTER study.

Bitzer M, Horger M, Giannini EG, Ganten TM, Wörns MA, Siveke JT, Dollinger MM, Gerken G, Scheulen ME, Wege H, Zagonel V, Cillo U, Trevisani F, Santoro A, Montesarchio V, Malek NP, Holzapfel J, Herz T, Ammendola AS, Pegoraro S, Hauns B, Mais A, Lauer UM, Henning SW, Hentsch B.

J Hepatol. 2016 Aug;65(2):280-8. doi: 10.1016/j.jhep.2016.02.043.

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SAPHIRE – Resminostat in Hodgkin’s Lymphoma

The SAPHIRE study was a multi-national, multi-center, single arm Phase II study to evaluate the efficacy, safety and pharmacokinetics of resminostat in patients with relapsed or refractory HL.

Recruitment status Completed
Study phase Phase II
Enrollment 37
Primary objective
  • Determine objective response rate (ORR)
Secondary objectives
  • Safety and tolerability of repeated oral doses of resminostat
  • Overall survival (OS)
  • Progression free survival (PFS) including radiological and symptomatic progression
  • Time to progression (TTP)
  • Pharmacokinetics of resminostat after oral dosing
Exploratory objectives
  • Investigate effects on histone deacetylase enzyme inhibition, histone acetylation and gene expression in peripheral blood mononuclear cells (PBMCs)
  • Investigate level of chemokine (C-C motif) ligand 17 (TARC) in blood plasma

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Combination of resminostat and docetaxel versus docetaxel in non-small cell lung cancer (NSCLC) in Japan and Korea

This study was a Phase I/II study to evaluate safety, tolerability and anti-tumor activity of resminostat in combination with docetaxel in pretreated Asian patients with NSCLC, conducted by our cooperation partner Yakult Honsha.

Recruitment status Completed
Study phase Phase I/II
Enrollment 9/108
Primary objective (Phase I)
  • Evaluate maximum tolerated dose (MTD) of resminostat in combination with docetaxel by investigating dose-limiting toxicity (DLT) and evaluate the recommended dose
Primary objective (Phase II)
  • Progression free survival (PFS)
Secondary objectives (Phase II)
  • Response rate (RR)
  • Overall survival (OS)
  • Safety parameters
Exploratory objectives (Phase II)
  • To evaluate biomarker and mRNA expression of the targeted genes in peripheral blood mononuclear cells (PBMCs)
Publication Phase I/II study of docetaxel combined with resminostat, an oral hydroxamic acid HDAC inhibitor, for advanced non-small cell lung cancer in patients previously treated with platinum-based chemotherapy.

Tambo Y, Hosomi Y, Sakai H, Nogami N, Atagi S, Sasaki Y, Kato T, Takahashi T, Seto T, Maemondo M, Nokihara H, Koyama R, Nakagawa K, Kawaguchi T, Okamura Y, Nakamura O, Nishio M, Tamura T.

Invest New Drugs. 2017 Jan 30. doi: 10.1007/s10637-017-0435-2. [Epub ahead of print]

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SHORE – Combination of Resminostat and FOLFIRI in Colorectal Cancer (CRC)

The SHORE study was a national, multi-center Phase I/II study to evaluate safety, tolerability, pharmacokinetics and efficacy of resminostat in combination with a second-line treatment in patients with K-ras mutated advanced CRC. The Phase II part of the study was not conducted.

Recruitment status Completed
Study phase Phase I/II
Enrollment 17
Primary objective
  • Evaluate maximum tolerated dose (MTD) of resminostat in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics
Secondary objectives
  • Progression free survival (PFS)
  • Objective response rate (ORR)
  • Time to progression (TTP)
  • Overall survival (OS)

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Resminostat in Japanese patients with advanced solid tumors

This study was a mono-center, single arm Phase I study of resminostat in Japanese patients with solid tumors, conducted by our cooperation partner Yakult Honsha.

Recruitment status Completed
Study phase Phase I
Enrollment 12
Primary objective
  • Evaluate safety of resminostat administered as monotherapy in patients with solid tumors
Secondary objectives
  • Investigate pharmacokinetic and pharmacodynamic characteristics of resminostat to determine recommended dose
  • Efficacy assessments measured by response rate (RR) and disease control rate (DCR)
Publication A phase I study of resminostat in Japanese patients with advanced solid tumors.

Kitazono S, Fujiwara Y, Nakamichi S, Mizugaki H, Nokihara H, Yamamoto N, Yamada Y, Inukai E, Nakamura O, Tamura T.

Cancer Chemother Pharmacol. 2015 Jun;75(6):1155-61. doi: 10.1007/s00280-015-2741-8.

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First-in-human study of resminostat in advanced solid tumors

This study was a first-in-human, mono-center, single arm, open label, dose escalation study of resminostat in patients with advanced solid tumors.

Recruitment status Completed
Study phase Phase I
Enrollment 19
Primary objectives
  • Investigate safety and tolerability of repeated ascending oral doses of resminostat
  • Determine maximum tolerated dose (MTD) and dose-limiting toxicities (DLT)
  • Assess pharmacokinetics of resminostat to evaluate optimal dose scheduling for further studies
Secondary objectives
  • Assess pharmacodynamics of once-daily and, as the study progresses, twice-daily dose administration
  • Investigate effects on histone deacetylase enzyme inhibition, histone acetylation and RNA profile
  • Evaluate potential anti-cancer activity
Publication First-in-human, pharmacokinetic and pharmacodynamic phase I study of Resminostat, an oral histone deacetylase inhibitor, in patients with advanced solid tumors.

Brunetto AT, Ang JE, Lal R, Olmos D, Molife LR, Kristeleit R, Parker A, Casamayor I, Olaleye M, Mais A, Hauns B, Strobel V, Hentsch B, de Bono JS.

Clin Cancer Res. 2013 Oct 1;19(19):5494-504. doi: 10.1158/1078-0432.CCR-13-0735.

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TOPAS – First-in-human study of 4SC-202 in hematologic malignancies

The TOPAS study was a first-in-human, multi-center, single arm, open label, dose escalation study of 4SC‑202 in patients with advanced hematologic malignancies.

Recruitment status Completed
Study phase Phase I
Enrollment 24
Primary objectives
  • Evaluate safety and tolerability of repeated ascending oral doses of 4SC‑202
  • Determine maximum tolerated dose (MTD) and dose-limiting toxicities (DLT)
  • Determine pharmacokinetic profile
Secondary objectives
  • Assess potential anti-cancer activity
  • Objective response rate (ORR)
  • Duration of response (DOR)
  • Progression free survival (PFS)
Exploratory objectives
  • Histone deacetylase (HDAC) inhibition in peripheral mononuclear cells (PBMCs)
  • Histone acetylation in PBMCs
  • Gene expression analysis in peripheral blood
  • Cytokine and miRNA levels in blood plasma

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