CPI-0610, A BROMODOMAIN AND EXTRATERMINAL DOMAIN PROTEIN (BET)
INHIBITOR, IN COMBINATION WITH RUXOLITINIB, IN JAK-INHIBITOR-NAÏVE
MYELOFIBROSIS PATIENTS: UPDATE OF MANIFEST PHASE 2 STUDY
J
ohn Mascarenhas1, Claire Harrison2, Moshe Talpaz3, Andrea Patriarca4, Timothy Devos5, Francesca
Palandri6, Raajit Rampal7, Adam Mead8, Marina Kremyanskaya1, Joseph Scandura9, Tim Somervaille10,
Marielle Wondergem11, Nikki Granacher12, Ronald Hoffman1, Katarina Luptakova13, Jing Wang13, Jessica
Christo13, Gozde Colak13, James Shao13, Suresh Bobba13, Patrick Trojer13, Srdan Verstovsek14, Vikas
Gupta15 and Francesco Passamonti16
(1)Division of Hematology/Medical Oncology, Icahn School of Medicine at Mount Sinai, New York
(2)Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
(3)University of Michigan, Rogel Cancer Center, Ann Arbor
(4)Azienda Ospedaliero Universitaria Maggiore della Carità di Novara SCDU Ematologia, Novara, Italy
(5)Department of Microbiology and Immunology, Laboratory of Molecular Immunology (Rega
Institute), KU Leuven; Division of Hematology, University Hospitals Leuven, Leuven, Belgium
(6)Institute of Hematology "L. & A. Seragnoli", University of Bologna, Bologna, Italy
(7)Memorial Sloan Kettering Cancer Center, New York, NY, USA
(8)University of Oxford, Oxford, United Kingdom
(9)Weill Cornell Medical College, Cornell University, New York
(10)Cancer Research UK Manchester Institute & The Christie Hospital, Manchester
(11)Department of Hematology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, Netherlands
(12)Ziekenhuis Netwerk Antwerpen, Antwerp, Belgium
(13)Constellation Pharmaceuticals, Cambridge
(14)The University of Texas, MD Anderson Cancer Center, Houston
(15)Princess Margaret Cancer Centre, Toronto, Canada
(16)Division of Hematology, Department of Medicine and Surgery, University of Insubria, Varese, Italy
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
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. Approximately one third of JAKi naïve MF patients 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 mechanism of action may improve the outcome in MF pts. 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; other endpoints: safety, PK, changes in proinflammatory cytokines and bone marrow
morphology/fibrosis
As of 29 September 2020, 78 pts treated, 66 pts ongoing. Baseline characteristics: mean age:
67 years old (SD: 10); 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
SCIENTIFIC PROGRAMME
SESSION I
OPTIMIZING
CYTOREDUCTION
SESSION II
MANAGEMENT OF CML
WITH TKI
SESSION III
MPN RISK
STRATIFICATION
INCLUDING VASCULAR
EVENTS
DEBATE 1
INTERFERON ALPHA
SHOULD BE FRONT LINE
THERAPY IN ALL ET/PV
PATIENTS
ROUNDTABLE 1
INFECTIONS IN
MYELOPROLIFERATIVE
DISORDERS, INCLUDING
CML
ROUNDTABLE 2
PREGNANCY AND
PARENTING
DEBATE 2
ALLOGENEIC STEM CELL
TRANSPLANTATION
SHOULD BE CONSIDERED
THIRD LINE OPTION IN
CHRONIC PHASE CML
SESSION IV
EVOLVING THERAPIES
IN MYELOFIBROSIS
SESSION V
MANAGEMENT OF
ADVANCED AND UNUSUAL
DISEASE (MPN AND CML)
SESSION VI
TREATMENT FREE
REMISSION IN CML
KEYNOTE LECTURE
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FO R A POSTER
PRESENTATION
DISCLOSURES