New Protocol Title: A Phase 1/2, First-in-Human Study of theMenin-KMT2A (MLL1)Inhibitor Bleximenib in Participants with Acute Leukemia Previous study title: A First in Human Study of the Menin-KMT2A (MLL1) Inhibitor JNJ-75276617 in Participants with Acute Leukemia

Research summary

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.

Principal Investigator

Prof Paresh Vyas

Contact us

Email: orh-tr.earlyphasenurses@nhs.net

IRAS number

297789