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
2 other identifiers
interventional
225
9 countries
29
Brief Summary
This study is being conducted to evaluate the safety, tolerability, and 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 Sep 2023
Longer than P75 for phase_1
29 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
June 21, 2023
CompletedFirst Posted
Study publicly available on registry
July 7, 2023
CompletedStudy Start
First participant enrolled
September 25, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 29, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 29, 2028
March 24, 2026
March 1, 2026
4.4 years
June 21, 2023
March 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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 monotherapy and in combination with ruxolitinib
Up to 3 years and 60 days
Number of participants with TEAEs leading to dose modification or discontinuation
Number of participants with TEAEs leading to dose modification or discontinuation.
Up to 3 years and 60 days
Secondary Outcomes (14)
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 3 years and 60 days
Participants with MF with symptomatic anemia: Anemia Response
Up to 3 years and 60 days
Participants With ET: Response Rate
Up to 3 years and 60 days
Participants With ET: Mean change from baseline of total symptom score (TSS)
Up to 3 years and 60 days
- +9 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 as monotherapy 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 as monotherapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with 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 and ET as defined in the protocol.
You may not qualify if:
- Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
- Active invasive malignancy over the previous 2 years.
- Active HBV/HCV, HIV.
- History of clinically significant or uncontrolled cardiac disease.
- Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
- Laboratory values outside the Protocol-defined ranges.
- 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.
- Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
- 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 within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
- For TGBs only: Undergoing treatment with a potent/strong inhibitor or inducer of CYP 3A4/5 within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment, or expected to receive such treatment during the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (29)
Royal Brisbane and Women'S Hospital
Herston, Queensland, 04029, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 05000, Australia
Peter Maccallum Cancer Centre
Melbourne, Victoria, 03000, Australia
The Alfred Hospital
Melbourne, Victoria, 03004, Australia
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9, Canada
Hopital Maisonneuve-Rosemont, Montreal, Qc
Montreal, Quebec, H1T 2M4, Canada
Odense University Hospital
Odense C, 05000, Denmark
Sjaellands Universitetshospital
Roskilde, 04000, Denmark
Vejle Hospital
Vejle, 07100, Denmark
Institut Bergonie
Bordeaux, 33076, France
Chu Nimes
Nîmes, 30029, France
Hospital Saint Louis
Paris, 75010, France
Institut Gustave Roussy
Villejuif, 94805, France
University Medical Center Rwth Aachen
Aachen, 52074, Germany
Universitatsklinikum Halle (Saale)
Halle, 06120, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Aou Policlinico S. Orsola-Malpighi
Bologna, 40138, Italy
Azienda Ospedaliero-Universitaria Careggi (Aouc)
Florence, 50134, Italy
Fondazione Irccs Ca Granda Ospedale Maggiore
Milan, 20122, Italy
National Cancer Center Hospital East
Chiba-ken, 277-0882, Japan
Kagoshima University Hospital
Kagoshima, 890-8520, Japan
Osaka Metropolitan University Hospital
Osaka, 545-8586, Japan
Nippon Medical School Hospital
Tokyo, 113-8603, Japan
Mie University Hospital
Tsu, 514-0001, Japan
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitari I Politecnic La Fe
Valencia, 46026, Spain
Guys and St Thomas Nhs Foundation Trust
London, SE1 9RT, United Kingdom
The Christie Nhs Foundation Trust Uk
Manchester, M20 4BV, United Kingdom
University of Oxford
Oxford, OX3 7LE, United Kingdom
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
June 21, 2023
First Posted
July 7, 2023
Study Start
September 25, 2023
Primary Completion (Estimated)
February 29, 2028
Study Completion (Estimated)
February 29, 2028
Last Updated
March 24, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share