KEY TAKEAWAYS
- The KOMET-001 phase I/II trial aimed to determine the RP2D of ziftomenib in NPM1m and KMT2Ar R/R AML patients.
- The study measured CR, CRc, and ORR.
- The result demonstrated that ziftomenib exhibited promising efficacy and tolerability in heavily pretreated NPM1m AML patients, with durable remissions and infrequent resistance mutations.
Researchers aimed to determine the recommended phase 2 dose(RP2D) of ziftomenib in NPM1m and KMT2Ar relapsed/refractory(R/R) acute myeloid leukemia(AML) patients.
The study provided an update on 20 NPM1m patients treated with 600mg of ziftomenib. The median age was 70.5 years, with common co-mutations of FLT3 (30%) and IDH1/2 (40%). Patients had a median of 3.0 (r: 1–10) prior therapies, and 20% had undergone at least one prior stem cell transplant (SCT).
The complete remission (CR) rate was 35%, with 40% achieving composite CR (CRc) and an overall response rate (ORR) of 45%. The median time to the first response was 51 days. For patients achieving CRc, the median duration of response (DoR) was 8.2 months. About 2 patients(1 CR and 1 incomplete count recovery) underwent SCT, remaining in remission, with one receiving post-SCT ziftomenib maintenance therapy.
Molecular analyses indicated ziftomenib’s efficacy in clearing measurable residual disease (MRD) of target mutations (e.g., NPM1, FLT3, and IDH1). Treatment emergent adverse events (TEAE) occurred in 85% of patients, with 30% potentially related to treatment. The most common grade 3 or higher TEAEs were anemia (25%) and thrombocytopenia (20%). Differentiation syndrome occurred in 20% of cases, with most being grade 2.
A resistance mutation (MEN1-M327I) developed in 1 out of 29 patients, detected at cycle 4 day 28 (C4D28). Patient maintained stable disease through cycle 7. Ziftomenib exhibited continued efficacy against the T349M mutation, identified in two-thirds of patients who acquired menin gatekeeper mutations in a different menin inhibitor trial.
The result demonstrated that ziftomenib exhibited promising efficacy and tolerability in heavily pretreated NPM1m AML patients, with durable remissions and infrequent resistance mutations.
Source: https://clml-soho2023.elsevierdigitaledition.com/304/index.html
Clinical Trial: https://clinicaltrials.gov/study/NCT04067336
Erba H, Wang E, Issa G, Altman J, Montesinos P, DeBotton S, Walter R, Pettit K, Strickland S, Patnaik M, Kremyanskaya M, Baer M, Foran J, Schiller G, Ades L, Heiblig M, Berthon C, Grembecka J, Cierpicki T, Clegg B, Peterlin P, Rodriguez Arboli E, Salamero O, Papayannidis C, Nie K, Ahsan JM, Tabachri M, Corum D, Leoni M, Dale S, Fathi A. Activity, Tolerability, and Resistance Profile of the Menin Inhibitor Ziftomenib in Adults With Relapsed/Refractory NPM1-Mutated AML.
