Menin Inhibitor Developments Transfer Acute Myeloid Leukemia Panorama Ahead

In a dialog with CancerNetwork^® on the 2024 European Hematology Affiliation (EHA) Congress, Eunice S. Wang, MD, highlighted findings associated to the usage of novel menin inhibitors as a growth of curiosity within the acute myeloid leukemia (AML) house.

Particularly, Wang, chief of the Leukemia Service of the Division of Drugs at Roswell Park Complete Most cancers Middle in Buffalo, New York, mentioned information on revumenib as a remedy for these with KMT2A-rearranged illness as a part of the part 2 AUGMENT-101 examine (NCT04065399). Findings confirmed that the inhibitor elicited a whole response (CR) and CR with hematologic restoration (CRh) price of 23% (95% CI, 12.7%-35.8%) amongst 57 evaluable sufferers.¹ In line with Wang, these information could assist the applying searching for FDA approval for revumenib on this affected person inhabitants.

The FDA granted precedence overview to revumenib in KMT2A-rearranged acute leukemia in March 2024.² The company set a Prescription Drug Person Price Act date of September 26, 2024 for the agent.

Transcript:

There’s quite a lot of curiosity at this EHA for a novel class of brokers referred to as menin inhibitors. These are a probably new class of brokers that focus on particular subsets of AML that now we have not been in a position to particularly inhibit up to now, and people are sufferers which have acute leukemias, AML, in addition to ALL characterised by a KMT2A or MLL rearrangement, in addition to as much as one-third of [patients with] AML who’ve mutations in nucleophosmin 1, or NPM1.

Maybe essentially the most superior [menin inhibitor] is the drug revumenib, which is being developed by Syndax. They introduced up to date outcomes of a part 2 examine [NCT04065399] the place they checked out 57 sufferers with KMT2A-rearranged acute leukemias and demonstrated the security and the efficacy of their compound throughout this complete subset. They’d total response charges of fifty% to 60%, they usually had CR and CRh charges of 23% with manageable differentiation syndrome.¹ There was nonetheless some QTc prolongation. This drug goes up for FDA approval later in September 2024, and these information have been being introduced to substantiate their software for that.

We additionally noticed a number of newer inhibitors on the market, [including] one from [Johnson & Johnson], the place they’re doing monotherapy in addition to mixture [therapy]. We noticed the outcomes of revumenib mixed with venetoclax [Venclexta]/azacitidine within the Beat AML trial [NCT03013998] with response charges of 100% in a really small variety of sufferers, so this class of brokers, I imagine, is transferring ahead.³

References

1. Aldoss I, Issa GC, Thirman M, et al. Revumenib monotherapy in sufferers with relapsed/refractory KMT2AR acute leukemia: topline efficacy and security outcomes from the pivotal AUGMENT-101 part 2 examine. Offered on the 2024 European Hematology Affiliation (EHA) Congress; June 13-16, 2024; Madrid, Spain. Summary S131.
2. Syndax publicizes FDA precedence overview of NDA for revumenib for the remedy of relapsed/refractory KMT2Ar acute leukemia. Information launch. Syndax Prescription drugs Inc. March 26, 2024. Accessed June 25, 2024. https://tinyurl.com/s4uzvyaw
3. Zeidner J, Lin TL, Welkie R, et al. Section 1b examine of azacitidine, venetoclax, and revumenib in newly recognized older adults with NPM1 mutated or KMT2A rearranged AML: interim outcomes of dose escalation from the BEATAML Consortium. Offered on the 2024 European Hematology Affiliation (EHA) Congress; June 13-16, 2024; Madrid, Spain. Summary S134.