A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
1 other identifier
interventional
290
1 country
13
Brief Summary
This study is being conducted to evaluate the safety, tolerability, dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered as a Monotherapy or in Combination With Ruxolitinib in participants with myeloproliferative neoplasms.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2023
Longer than P75 for phase_1
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 30, 2023
CompletedFirst Posted
Study publicly available on registry
September 13, 2023
CompletedStudy Start
First participant enrolled
December 4, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 29, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 29, 2028
April 17, 2026
April 1, 2026
4.9 years
August 30, 2023
April 14, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of participants with Dose Limiting Toxicities (DLTs)
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Up to 28 days
Number of participants with Treatment-emergent Adverse Events (TEAEs)
Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug, including those leading to dose modification or discontinuation.
Up to 3 years and 60 days
Secondary Outcomes (16)
Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
Up to 3 years and 60 days
Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol
Up to 24 weeks
Participants with symptomatic anemia: Anemia Response as defined in the protocol
Up to 24 weeks
Participants with ET: Response using the revised IWG-MRT and ELN response criteria for ET
Up to 3 years and 60 days
Incidence of AEs, ECGs, vital signs, and clinical laboratory evaluation
Up to 3 years and 60 days
- +11 more secondary outcomes
Study Arms (7)
Part 1a Dose Escalation Cohort Disease Group A - with MF
EXPERIMENTALINCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) will enroll in this group.
Part 1a Dose Escalation Cohort Disease Group A - with ET
EXPERIMENTALINCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with essential thrombocythemia (ET) will enroll in this group.
Part 1a: Dose Escalation Cohort Disease Group B - with TGB-MF SubOpt R
EXPERIMENTALINCA033989 will be administered at a protocol defined starting regimen in 28- day cycles and will allow for the evaluation of INCA033989 in combination with ruxolitinib to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) exhibiting suboptimal response (SubOpt R) will enroll in this group.
Part 1b: Dose Expansion - with MF
EXPERIMENTALINCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group.
Part 1b: Dose Expansion - with TGB-MF SubOpt R
EXPERIMENTALINCA033989 will be administered as an add-on therapy in combination with ruxolitinibat at the RDE(s) identified during Part 1a. Participants with treatment Group B (TGB) MF SubOpt R will enroll in this group.
Part 1b: Dose Expansion - with ET
EXPERIMENTALINCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group.
Part 1c: Dose Expansion
EXPERIMENTALINCA033989 will be administered at the dose level found to exhibit an overall positive benefit/risk as monotherapy or as combination therapy with Ruxolitinib. Participants with myelofibrosis (MF) will enroll in this group. The participants enrolled in the monotherapy arm will be offered the option to crossover to combination therapy with ruxolitinib if a suboptimal response to monotherapy is observed after 12 weeks.
Interventions
INCA033989 will be administered at protocol defined dose.
Rux will be administered according to Prescribing Information/SmPC.
Eligibility Criteria
You may qualify if:
- Life expectancy \> 6 months.
- Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease).
- Existing documentation from a qualified local laboratory of CALR exon-9 mutation.
- Participants with MF or ET as defined in the protocol.
You may not qualify if:
- Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
- Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
- Participants with laboratory values exceeding the protocol defined thresholds.
- Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
- Active invasive malignancy over the previous 2 years.
- History of clinically significant or uncontrolled cardiac disease.
- Active or chronic HBV or active HCV or known history of HIV.
- Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease, with the exception of ruxolitinib for TGBs only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
- Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
City of Hope Medical Center
Duarte, California, 91010, United States
Stanford Cancer Institute
Palo Alto, California, 94304, United States
University of Miami Health System
Miami, Florida, 33136, United States
The University of Kansas Cancer Center
Westwood, Kansas, 66205, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Washington University School of Medicine
St Louis, Missouri, 63108, United States
Icahn School of Medicine At Mount Sinai
New York, New York, 10029, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Md Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Incyte Medical Monitor
Incyte Corporation
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 30, 2023
First Posted
September 13, 2023
Study Start
December 4, 2023
Primary Completion (Estimated)
October 29, 2028
Study Completion (Estimated)
October 29, 2028
Last Updated
April 17, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share