A multicenter study to assess efficacy, safety, and tolerability of ropeginterferon alfa-2b-njft in patients with essential thrombocythemia in the US and Canada: EXCEED-ET trial

No new drugs have been approved for essential thrombocythemia (ET) treatment since the anagrelide approval in 1997. Ropeginterferon alfa-2b-njft (ropeg) is approved for polycythemia vera, providing a rationale for its use in ET. Its current dosing schema requires dose up-titrations with 50 mcg every 2 weeks and takes approximately 20 weeks to reach a plateau. The goal of this study is to assess the efficacy and safety of ropeg in ET using a higher initial dose and accelerated titration (HDAC) regimen. This is a single-arm, multicenter study in the US and Canada. Patients with ET receive ropeg at 250 mcg on Day 0, 350 mcg at Week 2, and 500 mcg from Week 4 onward with flexibility of dose adjustment. The primary endpoint is: platelets ≤400×10 9 /L, white blood cells 10×10 9 /L, improvement or non-progression of spleen size or major symptoms, and absence of hemorrhagic or thrombotic events, at months 10 and 13. Secondary endpoints include molecular response, safety and tolerability. A total of 91 patients were enrolled with 77 (84.6%) patients in the US and 14 (15.4%) in Canada. The last patient was enrolled on March 28, 2024. JAK2 V617F was found in 52 (57.1%) patients while CALR and MPL mutations in 34 (37.4%) and 5 (5.5%), respectively. As of November 12, 2024, the discontinuation rate was 8.8%. The study results will be available in mid-2025. This study will provide efficacy, tolerability and safety, molecular response and quality of life data that will be critical in assessing ropeg for ET treatment. Clinical trial registration ClinicalTrials.gov , identifier NCT05482971.