Sumitomo Pharma America Reveals Nuvisertib and Enzomenib Data at 2024 ASH Meeting

Latest results from Phase 1/2 studies have shown potential for two investigational treatments targeting patients with relapsed or refractory blood and bone marrow cancers. Nuvisertib (TP-3654), an investigational oral small molecule selective PIM1 kinase inhibitor, is being evaluated in patients with relapsed/refractory myelofibrosis (MF). Another investigational treatment, enzomenib (DSP-5336), an oral small molecule designed to inhibit the menin and KMT2A protein interaction, is being tested in patients with relapsed/refractory acute leukemia.

Sumitomo Pharma America, Inc. (SMPA) presented this new clinical data at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition. The data supports further development of these treatments for specific blood and bone marrow cancers.

The Phase 1/2 study of nuvisertib monotherapy included 74 patients with relapsed/refractory MF. The findings indicated that nuvisertib was well tolerated, with no dose-limiting toxicities observed. Preliminary results in evaluable patients demonstrated clinical activity, including a 22.2% reduction in spleen volume, a 44.4% reduction in symptoms, improvements in bone marrow fibrosis (47.8% of patients), hemoglobin levels (25% of patients), and platelet counts (27.6% of patients). Additional data showed that nuvisertib treatment resulted in significant cytokine modulation, correlating with spleen and symptom responses. The study has been expanded to include nuvisertib in combination with ruxolitinib and momelotinib, both JAK inhibitors, to evaluate safety and clinical activity.

Dr. Joshua Zeidner from the University of North Carolina presented new clinical and translational data from the enzomenib Phase 1/2 study. The safety population comprised 84 patients with acute leukemia, most of whom had acute myeloid leukemia (AML). The study population was diverse, with a significant percentage of non-white patients (47.6%) and heavily pre-treated individuals, with a median of three prior regimens.

Enzomenib was administered twice daily in continuous 28-day study cycles, at doses ranging from 40 mg to 300 mg. The treatment was well tolerated with low rates of drug-related adverse events and no dose-limiting toxicity reported. Differentiation syndrome occurred in 10.7% of patients but did not lead to deaths or require permanent discontinuation of enzomenib.

The dose optimization cohorts, at 200 mg and 300 mg doses, showed promising clinical activity. Among 23 patients with KMT2Ar, the Objective Response Rate (ORR) was 65.2%, and 30.4% achieved CR+CRh. In the subset that received 300 mg BID, the ORR was 73.3%, with a CR+CR rate of 40%. Among 17 patients with NPM1 mutations who received 200 mg or 300 mg doses, the ORR was 58.8%, with 47.1% achieving CR+CRh. The ongoing 400 mg BID dose optimization cohort has enrolled 21 patients, with data expected to be presented at a future conference.

These encouraging results, combined with an excellent safety profile, suggest that enzomenib could play a significant role in treating patients with relapsed/refractory acute leukemia with KMT2A rearrangement or NPM1 mutation. SMPA's President and CEO, Tsutomu Nakagawa, expressed optimism about these findings, emphasizing the company's commitment to advancing nuvisertib and enzomenib. He highlighted the potential of these investigational therapies to improve the lives of patients with critical cancers who do not respond to current treatments.

Myelofibrosis is a rare blood cancer characterized by the buildup of fibrous tissue in the bone marrow, leading to disrupted blood cell production. This condition is linked to dysregulation in the JAK signaling pathway, with an incidence of 0.7 new cases per 100,000 people worldwide each year. Leukemia, a cancer that forms in blood-forming tissue, involves uncontrolled growth of blood cells, typically in the bone marrow. Acute leukemia, a severe form, requires immediate treatment due to its rapid progression and onset of symptoms. Approximately 30% of AML patients have NPM1 mutations, and 5-10% have KMT2A rearrangements.

SMPA's Chief Medical Officer, Jatin Shah, M.D., expressed encouragement from the promising clinical activity observed for both nuvisertib and enzomenib. He highlighted the potential for PIM1 inhibition in myelofibrosis and menin inhibitors in acute leukemia, reinforcing the need for new treatment options for these incurable cancers.