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WJ01024 alone and in combination with ruxolitinib was safe and generated efficacy signals in relapsed/refractory myelofibrosis.
Treatment with the XPO1 inhibitor WJ01024 alone or in combination with ruxolitinib (Jakafi) was well tolerated and yielded rapid, durable spleen responses and sustained constitutional improvements in patients with myelofibrosis who were relapsed/refractory or intolerant to a JAK inhibitor, according to data from a phase 1 trial (NCT06909136).1
Findings presented at the
In patients treated with WJ01024 at 60 mg plus ruxolitinib (n = 3), no grade 3 or higher TEAES, TEAEs leading to dose reduction, or serious AEs were reported.
Regarding efficacy (n = 15), 73.3% of patients experienced any reduction in spleen volume, and 57.1% achieved at least a 25% reduction in spleen volume (SVR25). In patients treated with WJ01024 at 60 mg plus ruxolitinib, the SVR25 and SVR35 rates were 100% and 66.7%, respectively. All 3 of these patients experienced at least a 50% reduction in total symptom score.
An overall trend in reduced symptom burden was also observed, noted by improvements in early satiety and abdominal discomfort. Furthermore, rapid and sustained drops in white blood cell counts and corresponding reductions in lactate dehydrogenase levels were observed across all dose levels.
“WJ01024 has shown considerable potential in treating myelofibrosis and is currently advancing in phase 2 clinical development,” lead study author Hu Zhou, MD, of the Department of Hematology at the Affiliated Cancer Hospital of Zhengzhou University, and colleagues wrote in a poster presentation of the data.
WJ01024 is a next-generation XPO1 inhibitor featuring a rapidly metabolizing pharmacokinetic profile that has demonstrated improved tolerability in cynomolgus monkeys and human testing. By targeting XP01, WJ01024 offers a unique treatment approach for patients who are intolerant or refractory to JAK inhibitors.2
The phase 1 study includes both monotherapy and combination arms during dose escalation in phase 1a, along with additional combination arms in continued dose escalation in phase 1b.2
Enrolled patients are required to have primary myelofibrosis, post–polycythemia vera myelofibrosis, or post–essential thrombocytopenia myelofibrosis in addition to intermediate-1–, intermediate-2–, or high-risk disease per Dynamic International Prognostic Scoring System (DIPSS) criteria. Palpable splenomegaly of at least 5 cm below the left costal margin or a radiologically confirmed spleen volume of at least 450 cm are required. Patients in phase 1a are required to have received a prior JAK inhibitor for at least 6 months and be relapsed/refractory or intolerant to treatment. Notably, patients naive to JAK inhibitors are being included in phase 1b.
During dose escalation in phase 1a, WJ01024 is being evaluated at 20 mg per week, 40 mg per week, 60 mg per week, and 80 mg per week, as well as in combination with ruxolitinib at 60 or 80 mg per week. In phase 1b, the 2 combination regimens being evaluated are using WJ01024 at 40 mg per week and 60 mg per week.
The study’s primary objectives are to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of WJ01024 alone and in combination with ruxolitinib.
In the evaluable population at data cutoff (n = 15), patients had a median age of 67 years (range, 36-78), and most were male (53.3%). The majority of patients had an ECOG performance status of 0 or 1 (86.7%) and had primary myelofibrosis (86.7%). DIPSS risk categories included intermediate-1 (46.7%), intermediate-2 (40%), and high (13.3%). Muations detected at baseline included JAK2 (73.3%), CALR (26.7%), and HMR (26.7%); no patients harbored MPL mutations. Patients also had a baseline spleen volume of 1710.8 cm3 (range, 833.5-3046.1).
Across all dose levels in both monotherapy and combination cohorts, all patients experienced treatment-related gastrointestinal TRAEs, including nausea (80.0%), vomiting (66.7%), constipation (33.3%), and diarrhea (20.0%). Other common TRAEs reported in at least 20% of patients included decreased weight (60.0%), decreased platelet count (60.0%), decreased white blood cell count (33.3%), increased alanine aminotransferase levels (26.7%), increased blood bilirubin levels (26.7%), decreased neutrophil count (20.0%), decreased fibrinogen levels (20.0%), decreased appetite (53.3%), hyperuricemia (40.0%), anemia (66.7%), asthenia (46.7%), dizziness (26.7%), and abnormal hepatic function (33.3%).
