Preliminary data shows lowered cytokine levels in myelofibrosis with PIM1 kinase inhibitor
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SAN DIEGO — Treatment with a selective PIM1 kinase inhibitor showed positive clinical reactions in a sample of 23 patients with relapsed/refractory myelofibrosis, according to preliminary data presented at ASH Annual Meeting.
TP-3654, an oral investigational highly selective PIM1 kinase inhibitor, is the subject of the phase 1/phase 2 study evaluating monotherapy in relapsed/refractory myelofibrosis, according to results published by a team led by Lindsay A.M. Rein, MD, a hematologic oncologist at Duke Cancer Center.
Elevated circulating cytokines have previously been noted as having a strong association with myelofibrosis, and preclinical studies evaluating TP-3654 as both a monotherapy and in tandem with ruxolitinib (Jakafi, Incyte) displayed lowered cytokine response and other responses, such as spleen reduction and bone marrow fibrosis reduction.
As such, the phase 1/phase 2 study further examined TP-3654 monotherapy in a cohort of patients with intermediate or high-risk myelofibrosis, and who had been previously treated with or were ineligible for JAK inhibitor treatment.
The 23 patients — who had a median age of 73 years and all but one of whom had previously received JAK inhibitor treatment — were monitored for cytokine changes over 12 weeks of TP-3654 monotherapy. “Broad reductions” in cytokine levels were observed in as little as 24 hours, and over the course of 12 weeks, patients with higher cytokine reduction levels were found to have greater reduction in symptoms.
Twelve of 13 eligible patients saw a reduction in their total symptom score, with seven having their score reduced by 50% or more. Treatment-related adverse events, such as nausea and vomiting, were observed in over 20% of patients.
Rein noted that enrollment is still ongoing.
Reference:
Rein LAM, 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. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2023; San Diego.
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