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Ref Type Journal Article
PMID (30347469)
Authors von Tresckow B, Sayehli C, Aulitzky WE, Goebeler ME, Schwab M, Braz E, Krauss B, Krauss R, Hermann F, Bartz R, Engert A
Title Phase I study of domatinostat (4SC-202), a class I histone deacetylase inhibitor in patients with advanced hematological malignancies.
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Abstract Text Domatinostat (4SC-202) is a selective class I histone deacetylase inhibitor (HDACi). This phase I study investigated safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity in patients with advanced hematological malignancies.Domatinostat was administered orally once (QD) or twice daily (BID) on days 1-14 with 7 days off or continuously days 1-21 in a 3 + 3 design at 7 dose levels from 25 to 400 mg total daily dose (TDD). Twenty-four patients were treated with domatinostat.No formal maximum tolerated dose (MTD) was determined. One dose-limiting toxicity (DLT, grade 4 hypercalcemia) occurred during 200 mg BID continuous treatment. Six patients were reported with ≥ grade 3 treatment-related adverse events (TRAE; grade 3 hematological in three patients, grade 3 and grade 4 liver enzyme increase in 2 patients, grade 4 pulmonary embolism, and grade 4 hypercalcemia in one patient each). Higher grade hepatic TRAE occurred in the 200 mg BID continuous treatment cohort. Out of 24 patients, 1 achieved a complete response, 1 achieved a partial response, and 18 had stable disease as best response.Administration of domatinostat was safe, well tolerated with signs of antitumor activity. Four hundred milligram TDD in a 200 mg BID schedule (14 + 7) is the recommended phase II dose for monotherapy.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Domatinostat Domatinostat 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Domatinostat 4SC-202 HDAC Inhibitor 45 Domatinostat (4SC-202) is a class I histone deacetylase inhibitor that inhibits proliferation and induces apoptosis in tumor cells (PMID: 26773495, PMID: 30347469, PMID: 32210076).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References