PACIFICA Investigates Pacritinib’s Ability to Reduce Spleen Volume in Myelofibrosis

Following PERSIST-1 and PERSIST-2 and a recent FDA approval, pacritinib is being investigated in a phase 3 study versus physician's choice of standard therapy in patients with myelofibrosis.

In the phase 3 PACIFICA clinical trial, the efficacy of pacritinib (Vonjo) is being compared with physician’s choice of therapy in patients with primary myelofibrosis, post polycythemia myelofibrosis, and post-essential thrombocytopenia myelofibrosis with severe thrombocytopenia.1

Pacritinib is an oral macrocyclic Janus kinase inhibitor used to inhibit JAK2IRAK1, and CSFIR. The agent was recently granted approval by the FDA for the treatment of patients with myelofibrosis and severe thrombocytopenia, defined as a platelet count less than 50x109/L.

In certain myelofibrosis subtypes, like patients with severe thrombocytopenia, patients have more frequent anemia and leukopenia, and higher rates of hemorrhagic and thrombotic complications. Moreover, compared with the over population of patients with myelofibrosis, those with severe thrombocytopenia have an overall survival (OS) of roughly 15 months. Ruxolitinib is standard-of-care treatment for these patients, but the treatment often requires dose reduction to levels that are less effective and there is no FDA approved dose for patients with severe thrombocytopenia.

Prior clinical activity was demonstrated with pacritinib in the phase 3 PERSIST-1 trial (NCT01773187) and PERSIST-2 trial (NCT02055781). Also, in the phase 2 dose-finding study PAC203, pacritinib was shown to be safe for patients with myelofibrosis and severe thrombocytopenia at 200 mg twice daily (BID).

In PACIFICA, investigators are administering pacritinib 200 mg BID orally or physician’s choice of either corticosteroids, hydroxyurea, danazol, or low-dose ruxolitinib (Jakafi) to 150 patients with myelofibrosis. The primary end point is the proportion of patients achieving a ≥35% spleen volume reduction, and secondary end points include total symptom score (TSS), OS, patients’ global impression of change, and the safety of pacritinib versus physician’s choice of therapy. Other outcomes explored in the study include SVR of ≥ 35%, best response in SVR, > 25% SVR, and multiple laboratory values.2

Patients aged 18 years or older are eligible to enroll given they have myelofibrosis with and average platelet count of < 50,000/µL at screening, are intermediate-1, intermediate-2, or high risk, have palpable splenomegaly ≥ 5 cm below the lower costal margin in the midclavicular line, and have a TSS of ≥ 10 on the MPN-SAF TSS 2.0 or a single symptom score of ≥ 5 or 2 symptoms of ≥ 3.

All patients who enroll are also required to have an ECOG performance status of 0 to 2, peripheral blast count of < 10% and other adequate laboratory test results, as well as adequate liver and renal function, and coagulation.

The study excluded patients whose life expectancy is less than 6 months in addition to those who have been previously treated with allogeneic stem cell transplant, splenectomy, splenic irradiation within the last 6 months, pacritinib, any myelofibrosis-directed therapy within 14 days prior to treatment day 1, more than one JAK2 inhibitor, an experimental therapy within 28 days prior to treatment day 1, and systemic treatment with a strong CYP3A4 inhibitor or a strong cytochrome P450 inducer within 14 days prior to treatment day 1. Patients are also excluded if they have comorbidities that may interfere with study treatment.

Enrollment to the study began in 2019 and is ongoing at sites in the United States, Canada Europe, Asia, and the Middle East.

Reference:

1. Harrison CN, Gerd AT, Kildajian JJ, et al. Pacifica: a randomized, controlled phase 3 study of pacritinib vs. physician's choice in patients with primary myelofibrosis, post polycythemia vera myelofibrosis, or post essential thrombocytopenia myelofibrosis with severe thrombocytopenia (platelet count <50,000/mL). Blood. 2019; 134 (suppl 1): 4175. doi: 10.1182/blood-2019-129245

2. A phase 3 study of pacritinib in patients with primary myelofibrosis, post polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis (PACIFICA). Clinicaltrials.gov. Updated February 24, 2022. Accessed March 15, 2022.