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)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F25%3A00143866" target="_blank" >RIV/00216224:14110/25:00143866 - isvavai.cz</a>

Výsledek na webu

<a href="https://journals.lww.com/melanomaresearch/abstract/2025/08000/open_label_nonrandomized_phase_ib_study_to.5.aspx" target="_blank" >https://journals.lww.com/melanomaresearch/abstract/2025/08000/open_label_nonrandomized_phase_ib_study_to.5.aspx</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1097/CMR.0000000000001040" target="_blank" >10.1097/CMR.0000000000001040</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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)

Popis výsledku v původním jazyce

Tinostamustine is a first-in-class alkylating deacetylase inhibitor that facilitates access to cancer cell DNA, resulting in its damage and counteracting DNA repair systems. We hypothesize that the addition of tinostamustine to immune checkpoint inhibitors (ICIs) improves melanoma treatment. This open-label, nonrandomized phase IB study characterized dose-limiting toxicity (DLT) and the recommended dose (RD) of 2-weekly intravenous tinostamustine at escalating doses of 15 and 30 mg/m2 when administered with 2-weekly nivolumab 3 mg/kg added in cycle 2 in patients with melanoma. We included 17 patients (four at 15 mg/m2 and 13 at 30 mg/m2 tinostamustine). A total of 13/17 (77%) patients were ICI-resistant, 7/17 (41%) had unfavorable melanoma subtypes. No DLT was identified. Tinostamustine RD was 30 mg/m2 every 2 weeks. One patient experienced grade 2 nivolumab-associated immune-related pneumonitis. Tinostamustine-associated grade 3 leukocytopenia was documented in one patient, grade 2 leukocytopenia in five patients, and grade 1 thrombocytopenia in three patients. Treatment discontinuation occurred in one patient for nivolumab-associated immune-related pneumonitis and in another patient for tumor-related hemorrhage. A total of 7/13 (54%) evaluable patients had at least stable disease as best treatment response, including 3/13 (23%) patients with a confirmed partial response. 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.

Název v anglickém jazyce

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)

Popis výsledku anglicky

Tinostamustine is a first-in-class alkylating deacetylase inhibitor that facilitates access to cancer cell DNA, resulting in its damage and counteracting DNA repair systems. We hypothesize that the addition of tinostamustine to immune checkpoint inhibitors (ICIs) improves melanoma treatment. This open-label, nonrandomized phase IB study characterized dose-limiting toxicity (DLT) and the recommended dose (RD) of 2-weekly intravenous tinostamustine at escalating doses of 15 and 30 mg/m2 when administered with 2-weekly nivolumab 3 mg/kg added in cycle 2 in patients with melanoma. We included 17 patients (four at 15 mg/m2 and 13 at 30 mg/m2 tinostamustine). A total of 13/17 (77%) patients were ICI-resistant, 7/17 (41%) had unfavorable melanoma subtypes. No DLT was identified. Tinostamustine RD was 30 mg/m2 every 2 weeks. One patient experienced grade 2 nivolumab-associated immune-related pneumonitis. Tinostamustine-associated grade 3 leukocytopenia was documented in one patient, grade 2 leukocytopenia in five patients, and grade 1 thrombocytopenia in three patients. Treatment discontinuation occurred in one patient for nivolumab-associated immune-related pneumonitis and in another patient for tumor-related hemorrhage. A total of 7/13 (54%) evaluable patients had at least stable disease as best treatment response, including 3/13 (23%) patients with a confirmed partial response. 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

MELANOMA RESEARCH

ISSN

0960-8931

e-ISSN

1473-5636

Svazek periodika

35

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

252-258

Kód UT WoS článku

001519856300009

EID výsledku v databázi Scopus

2-s2.0-105004042259