A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05936359
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Incyte Corporation
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Incyte Medical Monitor
Principal Investigator Affiliation	Incyte Corporation
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, Canada, Denmark, France, Germany, Italy, Japan, Spain, United Kingdom
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Myeloproliferative Neoplasms

Arms & Interventions

Arms

Experimental: Part 1a Dose Escalation Cohort Disease Group A - with MF

INCA033989 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.

Experimental: Part 1a Dose Escalation Cohort Disease Group A - with ET

Experimental: Part 1a: Dose Escalation Cohort Disease Group B - with TGB-MF SubOpt R

INCA033989 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.

Experimental: Part 1b: Dose Expansion - with MF

INCA033989 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.

Experimental: Part 1b: Dose Expansion - with TGB-MF SubOpt R

INCA033989 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.

Experimental: Part 1b: Dose Expansion - with ET

INCA033989 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.

Experimental: Part 1c: Dose Expansion

INCA033989 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

Drug: - INCA033989

INCA033989 will be administered at protocol defined dose.

Drug: - Ruxolitinib

Rux will be administered according to Prescribing Information/SmPC.

Contact a Trial Team

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International Sites

Royal Brisbane and Women'S Hospital, Herston, Queensland, Australia

Status

Recruiting

Address

Royal Brisbane and Women'S Hospital

Herston, Queensland, 04029

Site Contact

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