TP-3654 Monotherapy Appears Safe, Effective in Relapsed or Refractory Myelofibrosis

Patients with relapsed or refractory myelofibrosis (MF) treated with TP-3654 monotherapy showed promising early signs in spleen volume reduction (SVR), total symptom score (TSS) improvement, and cytokine reductions, according to a study that will be presented at the 65th ASH Annual Meeting & Exposition, which is taking place December 9-12 in San Diego, California.

In this phase I/II trial, Lindsay Rein, MD, and colleagues assessed the safety and efficacy of the oral PIM1 kinase inhibitor TP-3654. They analyzed 23 patients with primary or secondary MF who were enrolled across 5 dose levels, and all but 1 patient received prior Janus kinase inhibitor treatment.

Over the 24-week treatment period, the investigators observed that hemoglobin and platelet counts remained stable. SVR was observed in 77% of evaluable patients treated for ≥12 weeks, and 3 patients showed ≥35% SVR. TSS was observed in most (92%) of the evaluable patients, and 7 patients showed ≥50% TSS response, while 5 had durable response for ≥12 weeks.

Using principal component analysis, researchers assessed the patterns of similarity of 43 cytokine changes after 12 weeks of treatment. They observed reductions in cytokines associated with MF (IL-8, IL-18, CD40, ENRAGE, and so on) within 24 hours of treatment, which was correlated with greater TSS improvement at week 12.

Moreover, the investigators observed that bone marrow fibrosis was reduced in 1 patient who achieved spleen and symptom responses, showed cytokine reductions, and had been on active treatment for 2 years. In total, ≥20% of patients experienced treatment-related adverse events, including grade 1/2 nausea, vomiting, and diarrhea. One patient experienced grade 3 diarrhea, and 2 experienced grade 3 platelet count decrease. No dose-limiting toxicities were observed in this analysis.

Reference

Rein L, El Chaer F, Yuda J, et al. Phase 1/2 study of TP-3654, a selective PIM1 kinase inhibitor: preliminary data showed clinical activity and cytokine reductions in relapsed/refractory myelofibrosis patients. Abstract #626. Presented at the 65th ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, California.