Study of INCA036978 in Participants With Myeloproliferative Neoplasms

• INCA036978 (Drug): INCA036978 will be administered at protocol defined dose.
• Standard disease-directed therapy (Drug): A standard disease-directed therapy will be administered according to Prescribing Information/SmPC.

Primary outcomes

• Number of participants with Dose Limiting Toxicities (DLT)s in Part 1 [Up to 28 days]: Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
• Number of participants with Treatment-emergent Adverse Events (TEAEs) [Up to approximately 2 years]: Defined as adverse events AE (either reported for the first time or the worsening of a pre-existing event) occurring after the first dose of study drug and up to 60 days after last dose of study drug or until the start of a new disease-directed therapy, whichever occurs first.
• Number of participants with TEAEs leading to dose modification or discontinuation [Up to approximately 2 years]: Number of participants with TEAEs leading to study drug modifications (interruptions, dose reduction) or discontinuation.

Secondary outcomes

• Pharmacokinetics Parameter: Cmax of INCA036978 [Up to approximately 2 years]: Defined as maximum observed plasma concentration of INCA036978.
• Pharmacokinetics Parameter: Tmax of INCA036978 [Up to approximately 2 years]: Defined as the time to reach the maximum plasma concentration of INCA036978.
• Pharmacokinetics Parameter: Cmax,ss of INCA036978 [Up to approximately 2 years]: Defined as the maximum observed plasma concentration at steady state of INCA036978.
• Pharmacokinetics Parameter: Cmin,ss of INCA036978 [Up to approximately 2 years]: Defined as the minimum observed plasma concentration at steady state of INCA036978.
• Pharmacokinetics Parameter: AUC(0-t) of INCA036978 [Up to approximately 2 years]: Defined as the area under the concentration-time curve up to the last measurable concentration of INCA036978.
• Pharmacokinetics Parameter: AUC 0-∞ of INCA036978 [Up to approximately 2 years]: Defined as the area under the concentration-time curve from 0 to infinity of INCA036978.
• Pharmacokinetics Parameter: CL/F of INCA036978 [Up to approximately 2 years]: Defined as the apparent clearance of INCA036978.
• Pharmacokinetics Parameter: Vz/F of INCA036978 [Up to approximately 2 years]: Defined as the apparent volume of distribution of INCA036978.
• Pharmacokinetics Parameter: t1/2 of INCA036978 [Up to approximately 2 years]: Defined as the apparent terminal phase disposition half-life of INCA036978.
• For participants with myelofibrosis (MF): Percentage of participants achieving spleen volume reduction as defined in the protocol [Week 12 and Week 24]: Defined as percentage of participants with a protocol defined spleen volume reduction.
• For participants with MF and anemia: Anemia Response as defined in the protocol [Up to approximately 2 years]: For non transfusion-dependent (TD) participants: An Hb increase relative to baseline as defined in the protocol if non-TD at baseline. For TD participants: Achieving transfusion independency (TI) as defined in the protocol.
• For participants with polycythemia vera (PV): Peripheral blood count remission as defined by the protocol. [Up to approximately 2 years]: Peripheral blood count remission as defined by the protocol.
• For participants with essential thrombocythemia (ET): Peripheral blood count remission as defined by the protocol. [Up to approximately 2 years]: Peripheral blood count remission as defined by the protocol.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Life expectancy > 6 months.
* Willingness to undergo a pretreatment and limited on-study BM biopsies and aspirates (as appropriate to disease).
* Participants with MF, PV and ET as defined in the protocol.

Exclusion Criteria:

* Presence of any hematological malignancy other than MF, PV, or ET.
* Malignancy within the last 3 years prior to enrollment.
* Acute or chronic HBV, Active HCV or known HIV or tuberculosis infection.
* Clinically significant or uncontrolled cardiac disease.
* Has undergone any prior allogeneic stem-cell transplantation or such transplantation is planned in the next 6 months.
* Laboratory values outside the Protocol-defined ranges.
* Prior history of major bleeding or thrombosis within the last 3 months prior to study enrollment.
* Presence of chronic or current active infectious disease requiring systemic treatment.
* Treatment with an MPN-directed therapy (approved or investigational) within the per protocol threshold before the administration of study drug.
* Prior radiation therapy within 28 days before the first dose of study treatment.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

• Incyte Medical Monitor, Study director, Incyte Corporation