At the European Hematology Association (EHA) Congress, June 8–11, 2023, updated results were presented from the Phase l KOMMET-001 study establishing a recommended Phase ll dose (RP2D) for Kura Oncology’s menin inhibitor ziftomenib. The agent is being evaluated in relapsed/refractory (R/R) patients who have KMT2A-rearranged (KMT2ar) or NPM1-mutant (NPM1m) acute myeloid leukaemia (AML). Ziftomenib targets the menin-KMT2a protein-protein interaction that may occur in patients with KMT2ar or NPM1m genetic alterations. The aberrant protein complex is essential for regulating leukaemia-promoting gene expression. Thus, targeting menin may be an effective strategy for patients with high unmet needs.

The median age of RP2D patients in the study was 70.5 years (22–86 years). Of the patients, 30% had the FLT3 mutation, 40% had the IDH1/2 mutation, and 20% had both co-mutations. The median number of prior therapies was three (r: 1–10), with 20% having undergone at least one prior stem cell transplant. Updated results show 35% of NPM1m patients (n=20) receiving once-daily 600mg oral ziftomenib, achieved complete remission (CR), with an overall 40% gaining composite CR (CRc); 45% had an objective response (OR), with a median time to first response of 51 days (r: 26–225) and a median duration of response of 8.2 months for all patients achieving CRc. Measurable residual disease clearance of NPM1 and key co-mutations FLT3 and IDH1/2 was observed, as in at least two patients, co-mutations at baseline were undetectable after two cycles. As for safety, 85% had at least one Grade 3 or higher treatment-emergent adverse event (TEAE). The most frequent (20%) TEAEs Grade 3 or higher were anaemia (25%) and thrombocytopenia (20%). A resistant mutation, MEN1-M3271, developed in one of 29 patients, detected at the end of Cycle 4, but the patient maintained stable disease through Cycle 7. Another key finding observed is that ziftomenib remains effective against the T349M mutation, a common menin gatekeeper mutation. With positive data at hand, the company is initiating a single-arm Phase II registrational study to further evaluate ziftomenib in R/R NPM1m AML. According to GlobalData’s analyst consensus forecast, global sales for ziftomenib will reach $255m by 2029. The drug is currently being tested for expanded access in acute lymphocytic leukaemia, in addition to a planned study investigating the drug in combination with venetoclax in AML. Kura faces competition in the menin inhibitor market as the therapy is being developed to treat various indications. Kura’s chief competitor is Syndax Pharmaceuticals, whose menin inhibitor revumenib is being evaluated in several indications, one of which is R/R AML. It received fast track and breakthrough designation from the FDA and is poised to be first to market. GlobalData forecasts total sales from this drug class to exceed $1bn by 2029.