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)
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
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)
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
MELANOMA RESEARCH
ISSN
0960-8931
e-ISSN
1473-5636
Volume of the periodical
35
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
7
Pages from-to
252-258
UT code for WoS article
001519856300009
EID of the result in the Scopus database
2-s2.0-105004042259