MPN-336: MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of CPI-0610 and Ruxolitinib vs Placebo and Ruxolitinib in JAKi Treatment-Naïve Myelofibrosis Patients

Autor: Gozde Colak, Patrick Trojer, Srdan Verstovsek, Jeffrey S. Humphrey, John Mascarenhas, Jing Wang, Katarina Luptakova, Suresh Bobba, Claire N. Harrison, James Shao
Rok vydání: 2021
Předmět:
Zdroj: Clinical Lymphoma Myeloma and Leukemia. 21:S363
ISSN: 2152-2650
Popis: Context: CPI-0610 is a unique, first-in-class, oral, small-molecule inhibitor of BET proteins, designed to promote disease-modifying activity through selective gene regulation of key oncogenic, fibrotic, and inflammatory factors with potential to transform the standard of care in MF. JAKi are currently approved for treatment of MF, including ruxolitinib (rux) and fedratinib. Approximately one-third of JAKi-naive MF pts treated with rux (35%; 106 of 301) or fedratinib (37%; 35 of 96) achieved a spleen volume reduction ≥35% (SVR35) at 6–12 months. CPI-0610, a potential disease-modifying therapeutic agent with a novel MoA may improve the outcome in MF pts. Clinical activity of CPI-0610 in combination with rux in JAKi-naive MF pts observed in the phase 2 MANIFEST study was higher than with rux alone in historical phase 3 trials. Design: MANIFEST-2 is a global, phase 3, 1:1 randomized, double-blind, active-control study of CPI-0610 + rux vs placebo + rux in JAKi treatment-naive patients with primary MF, post-polycythemia-vera MF, or post-essential-thrombocythemia MF. Patients: Key eligibility criteria: DIPSS score ≥Int-1; platelet ≥ 100 x 109/L; spleen volume ≥ 450 cc by CT/MRI; ≥ 2 symptoms measurable (score ≥3) or a total symptom score (TSS) of ≥ 10 using the MFSAF v4.0; peripheral blast count Interventions: Double-blind treatment (CPI-0610 or matching placebo) will be administered QD for 14 consecutive days followed by a 7-day break, which is considered 1 cycle of treatment. Rux will be administered BID for all 21 days within each cycle. Main Outcomes Measures: Primary endpoint: SVR35 response at wk 24; key secondary endpoint: TSS50 response (≥50% reduction in TSS) at wk 24; other secondary endpoints: safety, PK, PD, bone marrow morphology/fibrosis, duration of SVR35 response, duration of TSS50 response, PFS, OS, conversion from transfusion dependence to independence, rate of RBC transfusion for the first 24 wks, hemoglobin response, and peripheral proinflammatory cytokines.
Databáze: OpenAIRE
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