KTX-1001, a novel oral inhibitor of NSD2, demonstrates early clinical activity and manageable safety in heavily pretreated multiple myeloma.
In an interview with Pharmacy Times, Saad Usmani, MD, MBA, FACP, FASCO, myeloma specialist and cellular therapist at Memorial Sloan Kettering Cancer Center, discussed updated results from a Phase 1 clinical trial of KTX-1001 (Gintamatostat; K36 Therapeutics), a first-in-class oral selective inhibitor of MMSET/NSD2.
“Getting these kinds of disease responses tells us that we have activity, and now the idea would be to combine this treatment with other therapies to see if we can get better outcomes for our patients.” - Saad Usmani, MD, MBA, FACP, FASCO
Usmani explained that NSD2 is overexpressed in approximately 10% to 15% of newly diagnosed multiple myeloma patients with the t(4;14) translocation—a biologically distinct and more aggressive subtype. By inhibiting the catalytic SET domain of NSD2, KTX-1001 induces epigenetic reprogramming of myeloma cells and downregulates oncogenic signaling.
The Phase 1 study enrolled heavily pretreated, relapsed or refractory multiple myeloma patients who had received at least three prior lines of therapy, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies. The oral agent was administered twice daily, beginning with low doses to assess safety and tolerability. Among the 40 patients treated so far, hematologic adverse events—primarily thrombocytopenia—were most common. Non-hematologic grade 3 or higher events, including infection (12.5%) and fatigue (10%), were infrequent.
Importantly, Usmani noted early signs of clinical activity, including stable disease, minimal responses, and even very good partial responses in both t(4;14) and non-t(4;14) patients, some maintained beyond 12 months. He emphasized the potential of KTX-1001 as a targeted therapy for a specific myeloma subtype, differentiating it from broader treatments such as monoclonal antibodies, bispecifics, and CAR T-cell therapies. The future focus includes combination strategies with proteasome inhibitors, immunomodulators, or other immune therapies to enhance outcomes in this difficult-to-treat population.
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