Recipient organisationNIHR Wellcome Trust UCL Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Ongoing
In plain English
AI plain-English summary
A new oral drug called bleximenib is being tested for the first time in humans against aggressive leukaemias that have run out of treatment options. The problem is stark: patients whose acute leukaemia carries mutations in the KMT2A or NPM1 genes face particularly fast-progressing disease, and many cannot tolerate standard chemotherapy because of its high toxicity. Survival rates for these patients are poor, and existing treatments are limited. Bleximenib works by blocking the Menin-KMT2A protein interaction that drives these cancers, offering a targeted approach rather than a blanket cell-killing one. If the drug proves safe and effective in this Phase 1/2 trial, it could provide a new oral treatment option for patients with relapsed or refractory acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) who currently have few alternatives. The study will first determine the right dose in about 50 participants, then test safety and activity in a further 60. Success would not cure all patients, but it would add a much-needed tool for a group that is currently hard to treat.
View original technical description
This is a first-in-human (FIH), open-label, non-randomised, multicentre, Phase 1 study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of JNJ-75276617 (the study medication) in adult participants with relapsed or refractory acute leukaemia harbouring KMT2A or NPM1 gene alterations. Leukaemia (cancer of the white blood cells) is diagnosed as acute leukaemia when it progresses quickly and aggressively, and usually requires immediate treatment. Acute leukaemia is classified according to the type of white blood cells affected: Acute myeloid leukaemia (AML), which effects the myeloid cells that fight bacterial infections and other conditions, and acute lymphoblastic leukaemia (ALL), which effects the lymphoblastic cells that fight viral infections. KMT2A or NPM1 gene alterations are associated with aggressive acute leukaemias, both lymphoblastic and myeloid. Treatment options for AML and ALL are limited, survival rates are poor, and many patients are ineligible for standard chemotherapy treatments due to the high treatment-related mortality.The study will be conducted in 2 parts. Part 1 of the study will focus on dose escalation to determine the recommended Phase 2 dose(s) (RP2Ds) of the study medication. Doses will escalate (i.e. increase) based on the data gathered during the trial (including PK, PD, safety and preliminary clinical activity). Part 2 of the study will focus on dose expansion to determine the safety and tolerability at the RP2D(s). The study medication (which is administered orally as a tablet) will be administered once daily on a 28-day cycle during treatment. Approximately 110 participants may be treated (50 in Part 1, 60 in Part 2), however the actual sample size will depend on the number of cohorts explored during dose escalation and the size of the dose expansion cohorts.The study will consist of a Screening Phase, a Treatment Phase, and a Post-Treatment Follow-up Phase.
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