An investigation of the efficacy and safety of ropeginterferon alfa-2b-njft (P1101) in patients with essential thrombocytopenia (ET) is underway in the phase 3 SURPASS-ET study (NCT04285086).1
Currently, therapies available for the treatment of the chronic myeloproliferative neoplasm aim to control platelet and white blood cell counts, reduce the risk of hemorrhage, and prevent transformation to post-ET myelofibrosis or secondary acute myeloid leukemia. The standard-of-care treatment with these capabilities is hydroxyurea (HU), but research shows that 20% of patients with ET become intolerant or resistant to HU, underscoring a need for novel treatment options.
There have been a limited number of studies aiming to address HU intolerance and resistance in patients with ET. However, multiple novel therapies are in development, including ropeginterferon alfa-2b-njft.
“Long-acting interferons are clearly active in treating ET, impacting MPN stem cell and mutant allele burden. Although long-acting interferons are in our guidelines, they are not yet FDA approved and this crucial phase III trial is essential for confirming the efficacy and safety of ropeginterferon alfa-2b-njft for ET, and hopeful broaden availability for patients in ET as it has for PV," Ruben A. Mesa, MD, FACP told Targeted Oncology™.
About the SURPASS-ET Study
Trial Name: A Phase 3, Open-Label, Multicenter, Randomized, Active-controlled Study to Assess Pharmacokinetics and Compare the Efficacy, Safety, and Tolerability of P1101 vs Anagrelide as Second Line Therapy for Essential Thrombocythemia
ClinicalTrials.gov Identifier: NCT04285086
Sponsor: PharmaEssentia
Recruitment Contact: Toshiaki Sato, MD/PhD, +81 3 68669531, toshiaki_sato@pharmaessentia.com, or TingFang Wang, MS/MHA, +886 2 26557688 ext 7890, tingfang_wang@pharmaessentia.com
Completion Date:January 2024
SURPASS-ET, an open-label, multicenter, randomized, active-controlled study aims to investigate the drug further by comparing it with anagrelide as a second-line treatment for patients with ET. The study will begin with a 4-week screening period to identify patients with high-risk ET who are > 60 years of age and are JAK2 V617F-positive at the time of screening. Patients are required to have documented resistance of intolerance to HU and have completed HU washout 7 days or more before screening. Patients are also required to be naïve to treatment with interferon (IFN) or be anti-P1101-antibody-negative with IFN washout 14 days or more before screening.
Within the first 4 weeks of the study, investigators will exclude patients who are pregnant or lactating, have significant cardiovascular disease, documented autoimmune disease, history or presence of clinically significant depression or neurological disease, or other conditions that may interfere with safety of effectiveness of study treatment.
Between day 0 and week 52, patients in the study will receive ropeginterferon alfa-2b-njft at a starting dose of 250 mcg, followed by 350 mcg starting at week 2, and 500 mcg at week 4 and beyond. Study visits take place every 2-3 weeks or 4 weeks during the extension period of the study. Some visits may be telephone visits.
Investigators of SURPASS-ET are assessing several primary end points, including peripheral blood county remission, improvement or non-progression in disease-related signs, improvement in large symptoms or maintenance of non-progression, and the absence of hemorrhagic or thrombotic events. The secondary end points of the study include durable response at months 3 and 6, longitudinal rate, response rate at 3, 6, 9, and 12 months, occurrence of thromboembolic events over 12 months, time to first peripheral blood count response, duration of peripheral blood count remission response, symptomatic improvement, change in CALR, MPL, and JAK2 allelic burden over time, and improvement or non-progression of spleen size assessment. Another outcome of the study is bone marrow histological remission.
SURPASS-ET will also investigate several exploratory, safety, pharmacokinetic, and immunogenicity end points, including bone marrow histological remission, adverse events (AEs) and AEs of special interest, pharmacokinetic analysis and the relationship between exposure and efficacy/safety, the proportion of patients with and without antibody-drug antibodies, and neutralizing antibody in the ropeginterferon alfa-2b-njft treatment arm.
To conduct a comparison of the study outcomes between the 2 treatment arms, investigators will use a Cochrna-Mantel-Haenszel test. The study is 90% powered to detect an improvement in ELN response rate with ropeginterferon alfa-2b-njft (40%) vs anagrelide (15%).
To date, 161 patients with ET have been randomized in the SURPASS-ET study, according to baseline information. Of the patients enrolled, 154 are Asian, and 7 are Caucasian. The mean age of patients included in the study is 58.2 years, and the median age is 62 years. The study population is 46.6% male and 53.3% female. Over 80% of patients had a total symptom score < 20 at baseline.
The study is actively recruiting at 61 sites across 8 countries in North America and Asia.
“I hope we confirm the benefit of long-acting interferon for ET, and we build in combination approaches to deepen the impact that could lead to remissions. Additionally, further targeted approaches, such as targeting CALR are exciting and await these trials with great interest," said Mesa, president, Enterprise Cancer Service Line, executive director, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, enterprise senior vice president, Atrium Health, vice dean for Cancer Programs, Wake Forest University School of Medicine, professor of medicine, Wake Forest University School of Medicine.
REFERENCES:
Masarova L, Komatsu N, Gill H, et al. Surpass-ET: Ropeginterferon alfa-2b (P1101) vs anagrelide as second line therapy in essential thrombocythemia. Presented at: 11th Annual Meeting of the Society of Hematologic Oncology (SOHO 2023). September 8, 2023. Houston, TX. Abstract MPN-628.
