Key Clinical Summary:

• Design/Population: A phase 1 dose-escalation (3+3) study evaluated KTX1001, an oral selective NSD2 (MMSET) inhibitor, in ~ 40 patients with relapsed/refractory multiple myeloma, including t(4;14) and del(17p) subgroups; true monotherapy was administered without dexamethasone.
• Key Outcomes: Target engagement was demonstrated with early clinical activity observed in both t(4;14) and non-t(4;14) patients. The dose-limiting toxicity was thrombocytopenia, including grade 4 events at dose levels 8 to 9; no grade ≥ 3 non-hematologic AEs were reported.
• Clinical Relevance: KTX1001 shows promising on-target activity and manageable safety as a novel epigenetic therapy, particularly relevant for historically high-risk t(4;14) myeloma. Ongoing combination cohorts (with carfilzomib and mezigdomide) will further define its therapeutic potential.

Saad Usmani, MD, MBA, FACP, FASCO, Memorial Sloan Kettering Cancer Center, New York, New York, presented early results from a phase 1 dose-escalation study of KTX1001, an oral selective NSD2 (MMSET) inhibitor, among patients with relapsed/refractory (R/R) multiple myeloma (MM), including those with subgroups of high-risk t(4;14) disease at the 2025 ASH Annual Meeting & Exposition.

KTX1001 demonstrated target engagement and clinical activity across cytogenetic subgroups, with manageable safety. Thrombocytopenia was the primary dose-limiting toxicity at higher dose levels.

Transcript:

Hello, my name is Saad Usmani. I'm the chief of the myeloma service at Memorial Sloan Kettering Cancer Center. We just presented an oral abstract on a dose-escalation study with a compound called KTX1001, which is an oral selective NSD2 inhibitor.

Now, myeloma has many different subtypes based on translocations or hyperdiploidy by cytogenetic evaluation. The patients who have translocation 4;14 make up about 10 to 15% of the patients and historically have been a poor prognostic subgroup of patients. The MMSET pathway—MMSET is also known as NSD2—gets overexpressed by virtue of having this translocation 4;14.

KTX1001 is an inhibitor of NSD2, and we treated roughly 40 odd patients on this dose escalation study. It was a typical 3+3 kind of a design going up to dose level 9.

What we observed in this study was that the drug does hit the target and we are starting to see activity both in translocation 4;14 patients, as well as those patients who did not have translocation 4;14. About 19 out of the 40 patients had translocation 4;14, 4 out of 10 had deletion 17p. There was good clinical activity in these different subgroups.

In terms of the KTX1001 safety, the key feature was thrombocytopenia. It was also DLT event with grade 4 when patients got to the dose level 8 and dose level 9. Besides that, we did not see any major non-hematologic [adverse events] that were grade 3 or higher. Overall, I think the safety profile looks pretty good. As next steps for this compound’s development, there are cohorts of combining it with carfilzomib and mezigdomide are underway.

I do want to highlight lastly that this is the true monotherapy kind of dose escalation study. No dexamethasone was utilized in combination. Thank you.

Source:

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. Dec 6-9, 2025; Orlando, FL. Abstract: 654A