First Patient With AML Dosed With Novel Ziftomenib Plus Xospata

A novel menin inhibitor, ziftomenib, plus standard-of-care treatment has been given to the first patient in a phase 1 trial for some patients with acute myeloid leukemia (AML), according to a press release from Kura Oncology, the manufacturing company of ziftomenib.

The phase 1 KOMET-008 trial is evaluating the combination of ziftomenib and standard-of-care treatments, which include Xospata (gilteritinib), FLAG-Ida (combinations of chemotherapies) or low-dose cytarabine to treat patients with NPM1-mutant or KMT2A-rearranged AML.

Ziftomenib is a novel, once-daily drug that targets the menin-KMT24/MLL protein-to-protein interaction, Kura Oncology defines. The drug may address an unmet need in this patient population with genetically defined AML.

Xospata, according to the National Cancer Institute, is a type of tyrosine kinase inhibitor, which blocks certain proteins to prevent the cancer cells from growing.

Approximately 171 patients will be enrolled in the trial. Patients will be distributed into five different cohorts to receive oral ziftomenib plus one of the standard-of-care treatments, depending on whether they have an NPM1 mutation or a KMT2A rearrangement, the ClinicalTrials.gov listing stated. The purpose of this phase 1a portion of the study is to examine the safety and tolerability of each drug combination.

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In phase 1b of the trial, newly enrolled patients will receive the maximum dose tolerated based on one of the treatment combinations previous patients received in phase 1a of the study, the listing explained.

“Roughly half of patients with relapsed or refractory NPM1-mutant AML have co-occurring FLT3 mutations, and the prognosis for these patients is particularly poor,” Dr. Stephen Dale, chief medical officer of Kura Oncology, said in the press release. “Given the potential best-in-class safety and tolerability profile as well as the robust monotherapy activity observed in our phase 1 study of ziftomenib, we believe an all-oral combination of ziftomenib and [Xospata] may provide an attractive treatment option for these patients.”

According to Kure Oncology, the company is also conducting other studies to evaluate treatment combinations of ziftomenib with other standards of care for earlier lines of therapy in other patient populations.

KOMET-007, a phase 1 trial from Kura Oncology, began dosing patients with ziftomenib plus Venclexta (venetoclax) and Vidaza (azacitidine) in July 2023 for patients with relapsed/refractory NPM1-mutant and KMT2A-rearranged AML.

This drug combination was compared with standard induction chemotherapy in patients with NPM1-mutant and KMT2A-rearranged AML who have not received treatment before. In late January, the company announced that preliminary data from the trial was reflecting positive outcomes.

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AML is a type of leukemia that forms in the bone marrow and often moves quickly into the blood, according to the American Cancer Society. This form of cancer also develops from cells that typically become white blood cells, although AML can develop in additional types of blood-forming cells.

The American Cancer Society stated that in 2024 alone, there is an estimate of approximately 20,800 new cases of AML in adults. Although this type of leukemia is among the most common in adults, it is considered fairly rare and accounts for about 1% of all cancers.

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