Incyte to Discontinue Phase 3 LIMBER-304 Trial of Parsaclisib Plus Ruxolitinib in Myelofibrosis

The phase 3 LIMBER-304 trial (NCT04551053) evaluating parsaclisib plus ruxolitinib (Jakafi) in patients with myelofibrosis will be discontinued after results of a preplanned interim analysis conducted by an independent data monitoring committee indicated that the study is unlikely to meet its primary end point of targeted reduction in spleen volume in the intent-to-treat population, according to an announcement from Incyte.¹

The company noted that the decision to discontinue the trial was not related to safety. Incyte will inform investigators of the results and work with them to appropriately conclude the study in a manner consistent with the best interest of each patient.

Full data from the trial will be submitted for presentation at an upcoming medical meeting.

The randomized, double-blind LIMBER-304 trial was evaluating the safety and efficacy of parsaclisib in combination with ruxolitinib vs placebo plus ruxolitinib in patients at least 18 years of age with myelofibrosis who had an inadequate response to ruxolitinib monotherapy.

Patients were required to have primary myelofibrosis, post–polycythemia vera myelofibrosis, or post–essential thrombocythemia myelofibrosis who had intermediate-1, intermediate-2, or high risk per the Dynamic International Prognostic Scoring System (DIPSS).2 Other key inclusion criteria included treatment with ruxolitinib for at least 3 months with a stable dose for at least the last 8 weeks prior to day 1 of study treatment, a palpable spleen of at least 5 cm below the left costal margin on physical examination at screening, active symptoms of myelofibrosis at screening, an ECOG performance status of 0 to 2, and a life expectancy of at least 24 weeks.

Key exclusion criteria included prior therapy with any PI3K inhibitor; the use of experimental drug therapy for myelofibrosis or any other standard drug used for the disease other than ruxolitinib within 3 months of starting study treatment, lack of recovery from all toxicities from previous therapy (except ruxolitinib) to grade 1 or better, a recent history of inadequate bone marrow reserve, or inadequate liver and renal function at screening.

Enrolled patients were randomly assigned to receive oral parsaclisib once per day plus oral ruxolitinib twice per day, or oral placebo once per day plus oral ruxolitinib twice per day. Patients received parsaclisib or placebo starting on day 1 for the duration of the study, while continuing to receive ruxolitinib at the stable dose they were taking for 8 weeks prior to day 1. Patients were stratified by platelet count (≥ 100 × 109/L vs 50 to < 100 × 109/L) and DIPSS risk category (high vs intermediate-2 vs intermediate-1).

Treatment was unblinded at week 24. Those in the placebo arm had the opportunity to cross over to receive parsaclisib with continued ruxolitinib, as long as hematology parameters were determined to be acceptable.

Along with the primary end point of the proportion of patients to achieve targeted reduction in spleen volume by week 24, secondary end points included the proportion of patients who had a targeted reduction in total symptom score (TSS) from baseline to week 24, change in TSS from baseline to week 24, and time to first reduction of at least 50% in TSS from baseline to week 24. Other end points of interest included overall survival, safety, time to onset of targeted reduction in spleen volume, and duration of maintenance of targeted reduction in spleen volume.

References

1. 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. https://investor.incyte.com/news-releases/
2. To evaluate efficacy and safety of parsaclisib and ruxolitinib in participants with myelofibrosis who have suboptimal response to ruxolitinib (LIMBER-304). ClinicalTrials.gov. Updated December 5, 2022. Accessed March 6, 2023. https://clinicaltrials.gov/ct2/show/NCT04551053