ArticleJournal of hematology & oncology2025
Phase I first-in-human dose escalation study of the oral casein kinase 1α and cyclin dependent kinase 7/9 inhibitor BTX A51 in advanced MDS and AML.
Article in Journal of hematology & oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04872166 (An Open Label, Escalating Multiple Dose Study to Evaluate the Safety, Toxicity, and Pharmacokinetics of BTX A51 Alone and in Combination With Fulvestrant in Subjects With Advanced Solid Tumors and Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Metastatic Breast Cancer), which is not on this map. Cited by 3 papers.
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An Open Label, Escalating Multiple Dose Study to Evaluate the Safety, Toxicity, and Pharmacokinetics of BTX A51 Alone and in Combination With Fulvestrant in Subjects With Advanced Solid Tumors and Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Metastatic Breast Cancer
Who cites it
3 citing papers in PubMed.
- Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas.Clinical and experimental medicine · 2026Review
- Inhibition of CDK9 sensitizes multidrug resistant ovarian cancer cells to paclitaxel.Scientific reports · 2026Article
- Emerging strategies and novel therapeutic targets in acute myeloid leukemia: current advances and future directions.Biomarker research · 2025Review
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Authors and funding
16 authors.
Funding
Abstract
backgroundBTX A51, a first-in-class oral small molecule inhibitor of casein kinase 1α (CK1α) and cyclin-dependent kinase (CDK) 7 and 9, induces apoptosis of leukemic cells by activating p53 and inhibiting expression of Mcl1. Here, we report on the results of the phase 1 clinical trial of BTX A51 in patients with relapsed or refractory AML and MDS.
methodsAdult patients with R/R AML and high-risk MDS were enrolled into eight potential doses ranging from 1 to 42 mg dosed orally three days/week for 21 or 28 days out of a 28-day cycle. The maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of BTX A51 were investigated.
resultsThirty-one patients were enrolled and received treatment with BTX A51. Median age was 75 (range 22- 84) and 55% were male. Most patients (97%) had received prior treatment with venetoclax and hypomethylating agents. The most common treatment-emergent adverse events of any grade were nausea (67%), emesis (63%), hypokalemia (53%), and diarrhea (40%). Two patients experienced hepatic toxicity as DLTs, which resolved upon holding treatment. No treatment-related deaths occurred. The recommended phase 2 dose was 21 mg dosed three days/week for 4 weeks of a 28-day cycle. BTX A51 increased the expression of p53 and reduced the expression of MCL1 and RNA polymerase II phosphorylation in pre- and post-treatment immunocytochemistry studies. Overall, 3 patients (10%) experienced complete remission with incomplete count recovery (CRi). All 3 responding patients had RUNX1 mutations and the CR/CRi rate for RUNX1-mutated patients receiving BTX A51 at efficacious doses (11 mg or higher) was 30%. Ex-vivo studies confirmed higher efficacy of BTX A51 on RUNX1-mutated myeloblasts and demonstrated synergy with azacitidine and venetoclax.
conclusionsAlthough the overall efficacy was modest, this study lays the groundwork for future studies with improved patient selection and combination approaches.
trial registrationNCT04872166.
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