Recipient organisationNIHR University College London Hospitals Biomedical Research Centre
NIHR supportRecorded as supported by this research centre
PeriodMar 2025 — Dec 2026
In plain English
AI plain-English summary
A new oral drug, JNJ-75276617, is being tested for the first time in humans to treat aggressive leukaemias driven by specific genetic faults. This matters because patients with acute leukaemias carrying KMT2A or NPM1 gene alterations have very limited treatment options and poor survival rates. Many cannot tolerate standard chemotherapy due to its high toxicity. The drug works by blocking the interaction between two proteins, menin and KMT2A, that drive cancer growth in these genetic subtypes. The Phase 1 trial will enrol approximately 110 adults with relapsed or refractory disease across multiple UK centres. Part 1 determines the safest effective dose; Part 2 expands testing at that dose to confirm safety and early signs of activity. If successful, this could provide a targeted, oral therapy for patients who currently have few alternatives. It would not cure everyone, but it might offer longer remission and better quality of life for a group that urgently needs new options. The study is a necessary first step toward that possibility.
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.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know