POSTER 41
A PHASE 1 STUDY OF INCB057643 MONOTHERAPY IN PATIENTS WITH
RELAPSED OR REFRACTORY MYELOFIBROSIS (INCB 57643-103)
Pankit Vachhani1, Christine Lihou2, Gongfu Zhou2 and Fred Zheng2
(1)UAB Division of Hematology/Oncology, O'Neal Comprehensive Cancer Center at the UAB,
Birmingham, AL, USA
(2)Incyte Corporation, Wilmington, DE, USA
Background: Many neoplasms including myelofibrosis (MF) are associated with activation of
transcription factors that regulate oncogenic processes. These may respond to inhibition of
bromodomain and extra-terminal domain (BET) protein. In the first-in-human study INCB
57643-101, the BET inhibitor INCB057643, was generally safe and tolerable as monotherapy,
and demonstrated preliminary efficacy in patients with MF as monotherapy or combined with
the JAK inhibitor, ruxolitinib (Falchook G, et al. Clin Cancer Res. 2020). This phase 1, open-label,
two-part dose confirmation and expansion study further evaluates the safety and
tolerability of INCB057643 monotherapy in patients with relapsed/refractory MF (INCB 57643-
103; NCT04279847).
Methods: Eligible patients must be aged ≥18 years with histologically confirmed primary or
secondary MF (post-polycythemia vera, post-essential thrombocythemia), have received ≥1
prior therapy including ruxolitinib, have no known clinically beneficial therapy available, have
intermediate-2/high risk disease by Dynamic International Prognostic Scoring System, have
ECOG PS 0–2, life expectancy ≥24 weeks, and willing to provide a bone marrow biopsy and/or
aspirate at baseline (or archival sample obtained after most recent therapy). Exclusion criteria
include prior BET inhibitor or anticancer treatment within specified intervals before first dose;
concurrent anticancer therapy; allogeneic hematopoietic stem cell transplant (allo-HSCT) ≤6
months before enrollment; active graft versus host disease or immunosuppressive therapy
after allo-HSCT ≤2 weeks before first-dose; significant and uncontrolled disease (eg,
gastrointestinal, cardiovascular); history of bleeding disorders, high risk of bleeding, or
abnormal hematologic, hepatic, renal, coagulation, or metabolic laboratory values.
In part 1, ≤6 patients will receive oral INCB057643 4 mg once-daily continuously. Doses will be
deemed tolerable if ≤2 patients experience dose-limiting toxicities (DLTs) and ≤2 patients
discontinue due to treatment-related adverse events (TRAEs) during the DLT evaluation
period. Part 2 will further characterize safety and tolerability as well as evaluate preliminary
efficacy of INCB057643 in ≤9 patients. The starting dose will be 4 mg once-daily if tolerated in
Part 1, and 2 mg once-daily if not. Treatment may continue if clinically beneficial and
discontinuation criteria are not met.
The primary objective is to determine safety and tolerability of INCB057643 monotherapy.
Secondary objectives are to evaluate anemia response by International Working Group-
Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European
LeukemiaNet Consensus Report (ELN), transfusion dependence, spleen volume, rate and
duration of spleen response by IWG-MRT and ELN, and impact on quality of life. Patients will
be assessed every 3 cycles and will receive follow-up for safety for 30–35 days after last dose.
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