Bleximenib, Venetoclax, Azacitidine: AML Treatment Safety
bleximenib Combination Shows Promising Response Rates in Acute Myeloid Leukemia Subtypes
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New data presented at EHA highlights the potential of bleximenib in combination with venetoclax and azacitidine for patients with specific genetic alterations in acute myeloid leukemia (AML).
Recent findings from a Phase 1b study, presented at the European Hematology Association (EHA) Congress on May 7, 2025, indicate high response rates for bleximenib when combined with venetoclax and azacitidine in patients with relapsed/refractory (R/R) and newly diagnosed (ND) AML. The study focused on patients with specific genetic mutations, namely KMT2A rearrangements and NPM1 mutations, which are known to influence treatment outcomes.
Promising Efficacy in Key AML Subtypes
The combination therapy demonstrated important efficacy across both R/R and ND AML cohorts.
Relapsed/Refractory AML Cohort
In the R/R AML setting, participants treated with bleximenib at a dose of 100 mg plus venetoclax and azacitidine achieved an overall response rate (ORR) of 70.0% for those with KMT2A rearrangements. For patients with NPM1 mutations, the ORR was even higher, reaching 91.7%.
Newly Diagnosed AML Cohort
Similarly, in the ND AML cohort, the combination therapy yielded impressive results. Patients with KMT2A rearrangements experienced an ORR of 75.0%, while those with NPM1 mutations saw an ORR of 93.8%.
While these response rates are encouraging, the researchers noted that the small sample size makes it challenging to definitively conclude the precise impact of these genetic alterations on treatment response. Minimal residual disease (MRD) data is still pending,which will provide further insights into the depth of these responses.
Dosing and trial Integration
The data from the Phase 1b study has directly informed the recommended phase 2 dose (RP2D) for bleximenib in this combination regimen.
Recommended Phase 2 Dose (RP2D)
The totality of the clinical data has established bleximenib 100 mg twice daily as the RP2D when used in combination with venetoclax plus azacitidine for both R/R and ND AML patients harboring KMT2A rearrangements or NPM1 mutations.
Phase 3 Trial Design
This RP2D of bleximenib 100 mg twice daily is the proposed combination RP2D for the upcoming Phase 3 cAMeLot-2 trial. This placebo-controlled study will investigate the efficacy of venetoclax plus azacitidine with or without bleximenib in patients with ND AML who are ineligible for intensive chemotherapy. The trial is now open and actively enrolling participants.
Importantly, the findings from the Phase 1b study did not lead to any changes in the eligibility criteria for the Phase 3 trial.
Eligibility Criteria for Phase 3 cAMeLot-2 Trial
To be eligible for the cAMeLot-2 trial, participants must meet the following criteria:
Be aged 18 years or older. Have previously untreated ND AML.
Possess either KMT2A rearrangements or NPM1 mutations (defined as ≥10% blasts per 2022 International Consensus Classification criteria).
Be ineligible for intensive chemotherapy.
have adequate hepatic function.
Have a white blood cell count under 25 x 10^9/L.Key exclusion criteria include known active leukemic involvement of the central nervous system,a history of myelofibrosis,prior treatment with hypomethylating agents or chemotherapeutic agents for myelodysplastic syndrome,or significant cardiac disease.
The median number of cycles administered in the Phase 1b study for bleximenib 100 mg twice daily plus venetoclax plus azacitidine was 3 in both the R/R and ND settings. Notably, 22.7% of R/R patients and 10% of ND patients who received this combination proceeded to transplant, underscoring the potential of this regimen to bridge patients