A phase 3 study of revumenib plus venetoclax/azacitidine in adults with newly diagnosed NPM1 -mutated or KMT2A -rearranged acute myeloid leukemia ineligible for intensive chemotherapy (EVOLVE-2/HO177/AMLSG35-24/ACT-HOV-AML-002)
Abstract
TPS6600
Background:
Optimal treatment for patients (pts) with acute myeloid leukemia (AML) unfit for intensive chemotherapy (IC) remains challenging and depends on pt and disease characteristics and pt preference. In AML with a nucleophosmin-1 mutation (
NPM1
m) or lysine methyltransferase 2A (
KMT2A
) rearrangement (
KMT2A
r), menin-KMT2A fusion proteins upregulate
HOX/MEIS
gene expression, resulting in hematopoietic differentiation arrest and leukemogenesis. Revumenib is a first-in-class, oral, potent, and selective inhibitor of the menin-KMT2A interaction. In the phase 1/2 AUGMENT-101 study (NCT04065399), revumenib monotherapy demonstrated clinically meaningful response rates and was generally well tolerated in pts with relapsed/refractory
NPM1
m AML
or
KMT2A
r acute leukemia. To further improve outcomes, combination regimens are being studied as front-line therapy for newly diagnosed (ND) pts. In the phase 1b Beat AML study (NCT03013998), revumenib plus venetoclax/azacitidine (VEN/AZA) demonstrated deep responses in pts ≥60 years (y) of age with ND
NPM1
m or
KMT2A
r AML. EVOLVE-2 will assess whether revumenib plus VEN/AZA prolongs overall survival (OS) and improves complete remission (CR) rates in pts with ND
NPM1
m or
KMT2A
r AML ineligible for IC.
Methods:
EVOLVE-2 is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial (NCT06652438/EU-CT 2024-512733-32-00). Eligible pts are ≥75 y of age (18–74 y with comorbidities), have ND AML with centrally…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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