Novel Small Molecule Shows Early Activity in Pretreated Multiple Myeloma

In a conversation with CancerNetwork^®, Saad Z. Usmani, MD, MBA, FACP, FASCO, discussed preliminary efficacy and safety data from a phase 1 trial (NCT05651932) assessing the MMSET/NSD2 inhibitor gintemetostat (KTX-1001) among patients with heavily pretreated relapsed/refractory multiple myeloma. According to data presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition, the novel therapy demonstrated single-agent activity among patients with few remaining therapeutic options.

Usmani is a multiple myeloma specialist, cellular therapist, and chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center. He is also a member of the International Myeloma Foundation’s Scientific Advisory Board.

Transcript:

This clinical trial was a dose-escalation phase 1 study. Whenever we have a new drug, we must figure out the right [dose] to make sure it’s safe for patients. During that process, we also look at efficacy.

Roughly 40 patients were treated on the various cohorts. Almost half of the patients had t(4;14), the rest of the patients had other high-risk karyotypic abnormalities. This was a very heavily pretreated patient population. Most patients had more than 6 prior lines of treatment. They had seen a BCMA CAR T-cell therapy, bispecific [antibody], and a BCMA antibody drug conjugate [ADC]; almost 40% of the patients had received other non-BCMA bispecifics targeting GPRC5D or FcRH5. These patients did not have many options before they went on the study. What we observed both in t(4;14) and some non-t(4;14) [diseases] was durable control of disease, stable disease, minimal responses, and even 1 very good partial response in a [patient without] t(4;14).

The hematologic AEs were significant for thrombocytopenia, and about 30% of the patients had grade 3 or 4 [events]. The rates of neutropenia of grade 3 or higher were lower compared with what we would have expected for this patient population, roughly around 30%, but very well expected for what we would see here. In the non-hematologic AEs, interestingly, infection was not as common. Grade 3 infections were seen in about 12.5% of the patients, along with [grade 3] fatigue in about 10% of the patients. No other grade 3 or 4 events were observed as part of this study.

As an oral drug, this bodes well in general for the safety profile that we saw with the hematologic AEs. We’ll have to see as we combine this with other treatments how that signal emerges, but it appears to be consistent for what we would expect for this patient population.

Reference

Usmani S, Bories P, Gasparetto C, et al. Phase 1 study of ktx-1001, a first-in-class oral MMSET/NSD2 inhibitor, demonstrates clinical activity in relapsed/refractory multiple myeloma. Blood. 2025;146(suppl 1): 250. doi:10.1182/blood-2025-250