CPI-0610, A bromodomain and extraterminal domain (bet) protein inhibitor, in combination with ruxolitinib, in jak inhibitor-naive myelofibrosis patients: update of manifest phase 2 study
Palandri, F. Mascarenhas, J. Harrison, C. Patriarca, A. Devos, T. Rampal, R. Vannucchi, A. Passamonti, F. Mead, A. Kremyanskaya, M.
Palandri, F.
Mascarenhas, J.
Harrison, C.
Patriarca, A.
Devos, T.
Rampal, R.
Vannucchi, A.
Passamonti, F.
Mead, A.
Kremyanskaya, M.
Citations
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Abstract
CPI-0610 is first-in-class, oral, small-molecule inhibitor of BET proteins with potential for disease-modifying activity through altered gene
regulation of key oncogenic, fibrotic, and inflammatory factors and may
transform the standard of care in myelofibrosis (MF). CPI-0610 in combination with ruxolitinib (CPI-0610 +rux) is currently being studied in
JAK-inhibitor (JAKi) treatment-naïve MF patients (pts) in Arm 3 of
MANIFEST, a global, open-label, phase 2 study. Here we report the
safety and efficacy data from Arm 3 of the ongoing MANIFEST study.
Eligibility: JAKi-treatment-naïve MF pts with DIPSS score ≥Int-2;
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. Primary endpoint: SVR35 response (≥35% reduction in
spleen volume) at wk 24; key secondary endpoint: TSS50 response
(≥50% reduction in TSS) at wk 24. As of 29 September 2020, 78 pts
treated, 66 pts ongoing. Baseline characteristics: mean age: 67 years old;
72% male; primary MF: 54% pts; DIPSS ≥Int-2: 76% pts; IPSS ≥Int-2:
83%; 65% pts anemic (Hgb <10g/dL); median platelet: 294 x 109
/L
(range: 100, 1849); median spleen volume: 1719 cc (range: 451, 4782);
median TSS: 16 (range: 0, 38); high-molecular-risk mutations: 55% pts JAK2 mutation: 72%; ASXL1 mutation: 45%. At week 24, 67% (42/63)
pts achieved SVR35 (median % change from baseline: -50%; range: -
84.4%, 23.7%) and 57% (34/60) pts achieved TSS50 (median % change
from baseline: -59%; range: -100%, 225%). Additionally, 33% (16/48)
of pts had at least one grade improvement in bone marrow fibrosis. 78
pts were evaluable for safety. The most common hematological TEAEs
of any grade were anemia (33%, ≥Gr3: 30%) and thrombocytopenia
(32%, ≥Gr3: 8%). These cytopenias were generally manageable with
dose modifications. CPI-0610 + rux combination is generally well-tolerated in JAKi-treatment-naïve MF pts. The encouraging clinical data
demonstrate the potential for the combination treatment to provide enhanced efficacy as evidenced by higher SVR35 and TSS50 rates at wk
24 compared with historical data from pivotal phase 3 studies. Overall,
the data suggest that the addition of CPI-0610 to rux is potentially synergistic in JAKi-naïve MF pts. A phase 3, randomized, double blind, active-control study to further evaluate this combination is initiated.
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Palandri F, Mascarenhas J, Harrison C, Patriarca A, Devos T, Rampal R, et al. CPI-0610, A BROMODOMAIN AND EXTRATERMINAL DOMAIN (BET) PROTEIN INHIBITOR, IN COMBINATION WITH RUXOLITINIB, IN JAK INHIBITOR-NAIVE MYELOFIBROSIS PATIENTS: UPDATE OF MANIFEST PHASE 2 STUDY. Haematologica. 2021;106(10):5-6.