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TP-3654 Monotherapy Well-tolerated in Relapsed or Refractory Myelofibrosis

By Melissa Badamo November 30, 2023

Early signs of clinical activity such as spleen volume reduction (SVR), total symptom score (TSS) improvement, and cytokine reductions were seen in patients with relapsed or refractory myelofibrosis (MF) receiving TP-3654 treatment, according to a recent study.

Led by Lindsay Rein, MD, of Duke University, the goal of the phase I/II trial was to evaluate the safety and efficacy of the oral PIM1 kinase inhibitor TP-3654. Twenty-three patients with primary or secondary MF were enrolled across five dose levels, and all but one patient received prior JAK inhibitor treatment.

Throughout the 24-week treatment period, average hemoglobin and platelet counts remained stable. SVR was observed in 10 of 13 (77%) evaluable patients treated for ≥12 weeks, and three patients showed ≥35% SVR. TSS was observed in 12 of 13 (92%) evaluable patients, seven patients showed ≥50% TSS response, and five patients had durable response for ≥12 weeks.

Using principal component analysis (PCA), researchers also investigated the patterns of similarity of 43 cytokines changes after 12 weeks of treatment. Within the first 24 hours of treatment, researchers observed reductions in cytokines associated with MF (IL-8, IL-18, CD40, ENRAGE, etc), which was correlated with greater TSS improvement at week 12.

Bone marrow fibrosis was also reduced in one patient who achieved spleen and symptom responses, showed cytokine reductions, and is on active treatment for two years.

In terms of adverse events (AEs), ≥20% of patients experienced treatment-related AEs such as grade 1/2 nausea, vomiting, and diarrhea. One patient experienced grade 3 diarrhea and two experienced grade 3 platelet count decreased. There were no dose-limiting toxicities among patients.


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 and Exposition; December 9-12, 2023; San Diego, California.

Original Source: TP-3654 Monotherapy Well-tolerated in Relapsed or Refractory Myelofibrosis | Blood Cancers Today


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