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. 2025 Apr 17:12:1548590.
doi: 10.3389/fmed.2025.1548590. eCollection 2025.

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

Lucia Masarova  1 , Brandi N Reeves  2 , Firas El Chaer  3 , Lynda Foltz  4 , Tsewang Tashi  5 , Ghaith Abu-Zeinah  6 , Jennifer Lucas  7 , Anna B Halpern  8 , Dawn Maze  9 , Albert Qin  10 , Hana Safah  11 , Fengshuo Lan  12 , Casey L O'Connell  13 , Swati Goel  14 , Lindsay Rein  15 , Bruno Fang  16 , Joan How  17 , Sunil Babu  18 , Zhuoyan Li  19 , Sonia Cerquozzi  20 , Stephen T Oh  21 , Anthony M Hunter  22 , Nikolai Podoltsev  23 , Pankit Vachhani  24 , Abdulraheem Yacoub  25 , Julia M Cunningham  26 , Christopher Hillis  27 , Salman Otoukesh  28 , Oleh Zagrijtschuk  29 , Henry Castro  30 , Prithviraj Bose  1
Affiliations

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

Lucia Masarova et al. Front Med (Lausanne). .

Abstract

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 ≤400×109/L, white blood cells <10×109/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. JAK2V617F 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.

Keywords: clinical trial; complete hematologic response; essential thrombocythemia (ET); higher initial dose and accelerated titration (HDAC) regimen; molecular response; ropeginterferon alfa-2b-njft (ropeg).

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Conflict of interest statement

LM served on advisory boards for Cogent, GSK, MorphoSys, and PharmaEssentia. BR received consulting fees from PharmaEssentia, CTI BioPharma, and Incyte. FC serves as a consultant for SPD Oncology, Amgen, CTI BioPharma, AbbVie, MorphoSys, and the Association of Community Cancer Centers; received clinical trial grant support (PI) to the University of Virginia from Amgen, BMS, Celgene, SPD Oncology, Sanofi, Bristol Myers Squibb, FibroGen, PharmaEssentia, BioSight, MEI Pharma, Novartis, and Arog Pharmaceuticals; and received a travel grant from DAVA Oncology. LF received honoraria from AbbVie, BMS, GSK, Medison, and Novartis Research, and received funding from AbbVie, BMS, Constellation, CTI Biopharma, Incyte, PharmaEssentia, and Sumitomo Pharma. TT served as a consultant for Blueprint, PharmaEssentia, Cogent, and CITI Biopharma, and received funding from Blueprint, PharmaEssentia, Cogent, Italfarmaco, and Telios. GA-Z received research support from PharmaEssentia. DM received research support from Novartis, Celgene/BMS, PharmaEssentia, Takeda, and Kronos Bio, Inc.; received honoraria from Novartis, Celgene/BMS, and Jazz; served on advisory boards for Novartis, Celgene/BMS, and Jazz; and is a consultant for Pfizer and GSK. CO'C received research funding from Astex and Genentech and served on the scientific advisory board for GSK. AQ serves as chief medical officer of PharmaEssentia Corporation. LR received research funding from Kiadis Pharma. JH serves as a consultant for PharmaEssentia and Merck. SB received honoraria from Janssen Scientific Affairs, Pfizer, Novartis, and Cornerstone Healthcare Group; holds a consulting or advisory role with Cornerstone Specialty Network, E.R. Squibb Sons, LLC, Novartis, Kite (a Gilead company), Taiho Oncology, AstraZeneca, and Janssen Oncology; and received research funding: fromBristol-Myers Squibb, Novartis, Genentech/Roche, AstraZeneca/MedImmune, Janssen Oncology, Amgen, Abbvie, Lilly, Alexion Pharmaceuticals, Merck, Syndax, Nektar, Sanofi, Argenx, Gilead Sciences, BeiGene, Torl Biotherapeutics, 1200 Pharma, Takeda, Aptose Biosciences, and Aptose Biosciences. ZL holds a consulting or advisory role with AstraZeneca and Bristol Myers Squibb. SC served as a speaker and received honoraria from Novartis, Celgene, BMS, Incyte, Pfizer, Takeda, GSK, and Medison Pharma Canada Inc, and received consulting fees from Novartis, Celgene, BMS, Incyte, Pfizer, Abbvie, Medlior Health Outcomes Research, and Medison Pharma Canada Inc. StO served as a consultant for Kartos Therapeutics, CTIBioPharma, Celgene/Bristol Myers Squibb, Disc Medicine, Blueprint Medicines, PharmaEssentia, Constellation, Geron, Abbvie, Sierra Oncology, and Incyte. AHu received honoraria or consulting fees from GSK, Cogent Biosciences, PharmaEssentia, Blueprint Medicines, CTI Biopharma (now Sobi), and Incyte, and received research funding from Incyte, Cogent Biosciences, Ascentage Pharma, Blueprint Medicines, Syntrix Biosystems, Novartis, and PharmaEssentia. NP consulted for and received honoraria from Blueprint Medicines, Incyte, Novartis, PharmaEssentia, CTI BioPharma/Sobi, Constellation Pharmaceuticals/MorphoSys, AbbVie, Aptose Biosciences, and Karyopharm Therapeutics, and received honoraria as IDMC Chair from Cogent Biosciences. PV received consulting fees fromAbbVie, Amgen, Blueprint Medicines, Cogent Biosciences, Incyte, CTI BioPharma Corp, Daiichi Sankyo, GlaxoSmith Kline, Karyopharm, Novartis, Pfizer, Genentech, Servier, Stemline, MorphoSys, and LAVA Therapeutics, and honoraria for lectures/advisory boards from Incyte, Blueprint Medicines, and CTI Biopharma. AY provides consultancy for Incyte, CTI Pharma (SOBI), PharmaEssentia, Pfizer, Novartis, Servier, ABBVIE, Karyopharm Therapeutics, GSK, Blueprint Medicine, Apellis, Gilead, Notable Labs, and Protagonist, and received research funding from CTI Pharma (SOBI) and Stemline Therapeutics. JC received honoraria from Bioverativ (a Sanofi company), TrueNorth therapeutics, and CTI BioPharma. CH provided consultancy for Novartis, BMS, Abbvie, Beigene, Pfizer, and Eli Lilly. OZ works for PharmaEssentia USA. HC works for Everest, which is providing the CRO service for the EXCEED-ET study. PB consulted for or received honoraria from ABBVie, Blueprint, BMS, Cogent, CTI BioPharma Corp., (a Sobi company), Disc Medicine, Geron, GSK, Incyte, Ionis, Jubilant, Karyopharm, Keros, Morphic, MorphoSys, Novartis, Ono, PharmaEssentia, Raythera, and Sumitomo, and received research funding from Ajax, Blueprint, BMS, Cogent, CTI BioPharma Corp. (a Sobi company), DISC Medicine, Geron, Incyte, Ionis, Janssen, Kartos, Karyopharm, MorphoSys, Sumitomo, and Telios. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from PharmaEssentia. The funder had the following involvement in the study: study design, data collection and analysis. It was not involved in the decision to publish or preparation of the manuscript, outside of the work carried out by the authors.

Figures

Figure 1
Figure 1
Schematic study design.
See this image and copyright information in PMC

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