Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy
of INCB057643 as monotherapy or combination with ruxolitinib for participants with
myelofibrosis and other myeloid neoplasms.
Phase
Phase 1
Funding Agency/Sponsor
Industrial
Disease
Leukemia/heme
Enrollment Eligibility
Inclusion Criteria:
- Age 18 years and older at the time of signing the informed consent.
- Part 1: Relapsed or refractory MF, MDS, or MDS/MPN
a. Disease type:
•MF
- Primary MF or secondary MFs (post-PV MF, post-ET MF), histologically or cytologically
confirmed according to WHO 2016 criteria with measurable disease and risk category of
intermediate-2 or high according to DIPSS.
- Measurable disease is defined:
For dose escalation as having a palpable spleen of ≥ 5 cm below the left subcostal margin
(ribs).
- MDS
- Very low-, low-, intermediate-, or high risk MDS as per the IPSS-R criteria
- MDS/MPN
- Low-, intermediate-, or high-risk chronic myelomonocytic leukemia, atypical
chronic myeloid leukemia, MDS/MPN with ring sideroblasts and thrombocytosis, and
MDS/MPN unclassifiable as per the WHO 2016 criteria.
- Exception: Participants presenting with juvenile myelomonocytic leukemia will be
excluded.
b. Prior therapy
- Received at least 1 line of prior therapy; is refractory, relapsed, or intolerant
to the last therapy; and there is no further available therapy known to provide
clinical benefits, in the opinion of the investigator.
- Participants with MF must have received a JAK inhibitor(s) such as ruxolitinib.
- Part 2: MF - dose escalation and expansion
a. Disease type
- Primary MF or secondary MFs (post-PV MF, post-ET MF), histologically or
cytologically confirmed according to WHO 2016 criteria.
- Measurable disease is defined as having a palpable spleen of > 10 cm below the
left subcostal margin.
- 2 subgroups of participants in Part 2 - dose expansion will be enrolled:
- bone marrow myeloblast percentage between 5% (≥ 5%) and less than 20% (< 20%) or
myeloblast percentage ≥ 10% in peripheral blood in 2 occasions at least 2 weeks
apart.
b. Prior therapy
- Must currently be treated with ruxolitinib monotherapy at a stable dose for ≥ 8
weeks immediately preceding the first dose of study treatment.
- Must not be a candidate for potentially curative therapy, including hematopoietic
stem-cell transplantation.
- Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate at
screening/baseline, or archival sample obtained since completion of most recent
therapy.
- Willingness to avoid pregnancy or fathering children based on the criteria below.
Exclusion Criteria:
- Prior receipt of a BET inhibitor within 5 half-lives of the compound, and/or
experienced BET inhibitor-related AE(s) resulting in dose discontinuation.
Note: For participants in Part 2, ruxolitinib will continue at the participants' current,
ongoing doses. No ruxolitinib washout is needed.
- Concurrent anticancer therapy
- Participants who have received allogeneic hematopoietic stem cell transplantation
within 6 months of enrollment
- Active HBV or HCV infection or at risk for HBV reactivation.