P2, N=90, Not yet recruiting, SWOG Cancer Research Network

P2, N=6, Recruiting, Kyowa Kirin Co., Ltd.

The combination of ziftomenib 600 mg with venetoclax/azacitidine was well tolerated with deep and durable clinical activity in R/R NPM1-m AML. This trial was registered at www.ClinicalTrials.gov as #NCT05735184.

P1, N=0, Withdrawn, M.D. Anderson Cancer Center | N=32 --> 0 | Trial completion date: Dec 2034 --> May 2026 | Initiation date: Dec 2027 --> May 2026 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2032 --> May 2026

P2, N=88, Not yet recruiting, UNC Lineberger Comprehensive Cancer Center

Next, we show that inhibitors of SETD2 (EZM0414) and menin (Revumenib) have synergistic efficacy against MLL-fusion and NPM1-mut leukemia and make prominent induction of cell cycle arrest, differentiation, and apoptosis. Finally, we clarify that the combined-drug treatment delays MLL-fusion leukemia progression in vivo. Taken together, these findings establish the simultaneously blocking of transcription elongation and initiation by epigenetic inhibitors as a promising therapeutic strategy for these aggressive leukemias.

P1/2, N=263, Active, not recruiting, Kura Oncology, Inc. | Recruiting --> Active, not recruiting

P1, N=60, Active, not recruiting, Eilean Therapeutics | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2026 --> Apr 2026

P3, N=1300, Recruiting, Kura Oncology, Inc.

CRISPR base editor screening previously predicted several MEN1 (menin) mutations that have arisen in patients receiving SNDX-5613 and confer resistance...Co-crystal structures of menin bound to each menin inhibitor suggest resistance mechanisms related to how each inhibitor engages the KMT2A binding pocket of menin. Orthogonal in vitro and in vivo MEN1 mutation generation under therapeutic pressure suggest the MEN1 mutations identified with CRISPR base editor screening are likely to arise and impact all menin inhibitors.

P1, N=0, Withdrawn, Children's Oncology Group | N=29 --> 0 | Not yet recruiting --> Withdrawn

We evaluated RAS/MAPK targeting using the MEK1/2 inhibitor selumetinib in combination with the menin inhibitor revumenib. Our preclinical study suggests a potential targeted treatment combination for KMT2A-r and RAS pathway mutant leukemia, but one which will require further optimization. COG completed clinical trials AAML03P1, AAML0531, AAML1031 and C2961.