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 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 Chi-Joan How ¹⁷ Sunil Babu ¹⁸ Zhuoyan Li ¹⁹ Sonia Cerquozzi ²⁰ Stephen 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

• ¹ University of Texas MD Anderson Cancer Center, Houston, United States
• ² Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
• ³ Division of Hematology and Oncology, Department of Medicine, The University of Virginia, Charlottesville, United States
• ⁴ Division of Hematology, St. Paul’s Hospital, University of British Columbia, Vancouver, Canada
• ⁵ Huntsman Cancer Institute, School of Medicine, The University of Utah, Salt Lake City, Utah, United States
• ⁶ Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, New York, United States
• ⁷ Medical Oncology and Hematology, Marin Cancer Care, Greenbrae, United States
• ⁸ University of Washington Medical Center, Seattle, Washington, United States
• ⁹ Princess Margaret Cancer Centre, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
• ¹⁰ PharmaEssentia Corporation, Taipei, Taiwan
• ¹¹ Our Lady of the Lake College, Baton Rouge, Louisiana, United States
• ¹² Stony Brook University Medical Center, Stony Brook, United States
• ¹³ Keck School of Medicine, University of Southern California, Los Angeles, United States
• ¹⁴ Department of Hematology and Oncology, Montefiore Einstein Comprehensive cancer center, Albert Einstein College of Medicine, Bronx, United States
• ¹⁵ School of Medicine, Duke University, Durham, North Carolina, United States
• ¹⁶ Astera Cancer Care, East Brunswick, East Brunswick, United States
• ¹⁷ Dana Farber Cancer Institute/Massachusetts General Hospital, Boston, Boston, United States
• ¹⁸ Fort Wayne Medical Oncology & Hematology, Fort Wayne, United States
• ¹⁹ Greater Baltimore Medical Center, Baltimore, United States
• ²⁰ Division of Hematology and Hematologic Malignancies, University of Calgary, Alberta, Canada
• ²¹ Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, United States
• ²² Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, United States
• ²³ Hematology Section, Department of Internal Medicine, Yale School of Medicine, New Haven,, United States
• ²⁴ O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham, Birmingham, United States
• ²⁵ Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas, United States
• ²⁶ Division of Hematology-Oncology, Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, United States
• ²⁷ Department of Oncology, McMaster University, Hamilton, Canada
• ²⁸ Duarte, Duarte, United States
• ²⁹ PharmaEssentia USA, Burlington, United States
• ³⁰ Everest Clinical Research, Markham, Canada

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 two 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 endpoints are: platelets ≤400x10 9 /L, white blood cells <10x10 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. 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.