Parsaclisib Myelofibrosis Trial Discontinues; Likely To Miss Primary End Point

The phase 3 LIMBER-304 trial examining parsaclisib with ruxolitinib vs matched placebo will be discontinued after an interim analysis concluded it would likely miss the primary end point.

Investigators will discontinue treatment with parsaclisib plus ruxolitinib (Jakafi) for patients with myelofibrosis after an interim analysis concluded the regimen was unlikely to meet its primary end point, according to a press release on the phase 3 LIMBER-304 trial (NCT04551053).

Investigators will present data from the phase 3 LIMBER-304 trial evaluating parsaclisib plus ruxolitinib in myelofibrosis at a future medical meeting.

Investigators will present data from the phase 3 LIMBER-304 trial evaluating parsaclisib plus ruxolitinib in myelofibrosis at a future medical meeting.

LIMBER-304 examined the experimental regimen vs ruxolitinib monotherapy in patients with myelofibrosis who had an inadequate response to said monotherapy. In the interim analysis, an independent data monitoring committee assessed the intent-to-treat patient population.

Investigators will present data from this trial at a future medical meeting.

The randomized, double-blind phase 3 LIMBTER-304 study evaluated the combination regimen in an estimated 212 patients. Patients needed to be on stable doses of ruxolitinib ranging from 5 mg to 25 mg twice daily for at least 8 weeks prior to the first day of study treatment. They must also have received at least 3 months of prior ruxolitinib therapy overall.

Eligible patients were then randomly assigned 1:1 to receive either oral parsaclisib or matched placebo once daily in addition to continued ruxolitinib.

The primary end point was the incidence of targeted reductions in spleen volume as assessed by MRI or CT imaging. Secondary end points included the incidence of targeted reductions in total symptom score (TSS), overall changes in TSS, time to the first 50% or greater reduction in TSS, overall survival, the incidence of treatment-related adverse effects, the time of onset of spleen volume reductions, and the duration of maintenance of spleen volume reduction.

Stratification factors included platelet count and Dynamic International Prognostic Scoring System (DIPSS) risk category.

Patients needed to have disease which fell in the intermediate-1, intermediate-2, or high DIPSS risk categories to be included in the study. A palpable spleen of 5 cm or larger below the left costal margin on physical examination at the screening visit and an ECOG score no greater than 2 were also required for enrollment.

Available bone marrow biopsy specimens and pathology reports from 2 months prior or a bone marrow biopsy at screening were also required for inclusion. Patients also needed to have a life expectancy of at least 24 weeks.

Exclusion criteria included any prior therapy involving PI3K inhibition, as well as a recent history of inadequate bone marrow reserve or inadequate liver and renal function at screening. An active invasive malignancy in the preceding 2 years and splenic irradiation in the preceding 6 months before the first dose of the study drug were also grounds for exclusion.


Incyte provides update on interim analysis of phase 3 LIMBER-304 study of parsaclisib and ruxolitinib in patients with myelofibrosis. News Release. Incyte. March 3, 2023. Accessed March 6, 2023.

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