Early Findings on Ziftomenib With Chemotherapy in AML From KOMET-007 Trial

Ziftomenib plus standard cytarabine and daunorubicin chemotherapy was well tolerated with consistent safety and continued to show “robust clinical activity” in patients newly diagnosed with NPM1-mutated (NPM1-m) or KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML), according to an interim report from the ongoing KOMET-007 study.

The phase Ia findings were presented by Amer Zeidan, MBBS, MHS, of Yale University, at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

The interim analysis covered 34 patients,15 with high-risk NPM1-m AML and 19 with KMT2A-r AML. Of the 34 patients, 18 received ziftomenib 200 mg and 16 received ziftomenib 400 mg. The median follow-up was 33 and 18 weeks in the NPM1-m 200-mg and 400-mg groups and 22 and 12 weeks in the KMT2A-r 200-mg and 400-mg groups, respectively.

The most common grade 3 or higher treatment-emergent adverse events (TEAEs) in 20% or more of patients were febrile neutropenia (56%), decreased platelet count (47%), decreased neutrophil count (38%), anemia (32%), and decreased white blood cell count (29%).

Nine patients had grade 3 or higher AEs related to ziftomenib or chemotherapy including decreased platelet count (18%), decreased neutrophil count (15%), and anemia (9%). The authors reported that there were no cases of differentiation syndrome, ziftomenib-associated QTc prolongation, or dose-limiting toxicities (DLTs) with either dose level.

As of the June 2024 data cutoff, 15 patients in the NPM1-m group and 18 in the KMT2A-r had one or more response assessments. Among patients with NPM1-m AML, the composite complete response (CRc) rate was 100% in the 200-mg group (n=8/8) and 86% (n=6/7) in the 400-mg group. MRD negativity was reported in 100% (n=8/8) and 80% (n=4/5) of tested responders from the 200-mg and 400-mg groups, respectively.

Among patients with KMT2A-r AML, the CRc rate was 90% (n=9/10) in the 200-mg group and 63% (n=5/8) in the 400mg group. MRD negativity was reported in 83% (n=5/6) and 100% (n=3/3) tested responders from the 200-mg and 400-mg groups, respectively.

The overall CRc rate with both dose levels was 93% (n=14/15) for patients with NPM1-m AML and 78% (n=14/18) for those with KMT2A-r AML.

“Taken together, these data support the advancement of ziftomenib in combination with intensive chemotherapy,” Dr. Zeidan stated. “Updated results will be presented, as data from the 400 mg cohorts continue to mature and 600 mg cohorts are enrolling.”

 

Reference

Zeidan ZM, Wang ES, Issa GC, et al. Ziftomenib combined with intensive induction (7+3) in newly diagnosed NPM1-m or KMT2A-r acute myeloid leukemia: interim phase 1a results from KOMET-007. Abstract #214. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.