Phase 1 Trial Targets t(4;14) Population in Relapsed Multiple Myeloma

In an interview on the first-in-human phase 1 study of gintemetostat (KTX-1001), Saad Z. Usmani, MD, PhD, detailed the initial safety and efficacy findings for this oral therapy in patients with heavily pretreated, late-relapsed multiple myeloma. The study primarily focused on a dose-escalation protocol to determine the safety profile before shifting focus toward efficacy.

Patient Population and Characteristics

The trial involved approximately 40 patients across various dosing cohorts. This was an exceptionally "late-line" population, with a median of more than 6 previous lines of treatment. All participants were refractory to immunomodulatory drugs and proteasome inhibitors, and nearly all had previously received anti-CD38 monoclonal antibodies. Furthermore, the patient group had extensive exposure to advanced therapies: 40% had received BCMA-targeted CAR T-cell therapy, over 50% had received BCMA-directed bispecific antibodies or antibody-drug conjugates, and almost 40% had been treated with non-BCMA bispecifics, such as those targeting GPRC5D or FCRH5.

Safety Profile

From a safety perspective, the oral therapy was generally well-tolerated. Usmani noted that there were few non-hematologic adverse events of grade 3 or higher. The primary toxicities observed were hematologic, specifically grade 3 or 4 thrombocytopenia and some instances of neutropenia. Despite these occurrences, the drug was deemed safe to move through escalating dose cohorts.

Clinical Activity and Efficacy

Although the primary goal was safety, the trial yielded encouraging signals of clinical activity. Even at lower doses, some patients who had exhausted all standard-of-care options achieved stable disease or a response. Notably, clinical benefit was observed even in patients without the specific genetic translocation; although half of the patients carried the t(4;14) translocation, responses were seen in those without it as well. One standout case involved a patient achieving a very good partial response (VGPR) that was sustained for over 10 months. These results suggest that gintemetostat may provide a viable pathway for patients who are triple-class refractory and have failed modern BCMA-targeted interventions.