This study is being conducted to evaluate INCA033989 versus best available therapy in participants with essential thrombocythemia and a CALR mutation previously treated with cytoreductive therapy.

Inclusion Criteria:

• Confirmed diagnosis of high-risk ET.
• Presence of mutCALR.
• Prior treatment with at least 1 cytoreductive therapy.

Exclusion Criteria:

• Presence of any hematologic malignancy other than ET.
• Major bleeding or thrombosis within the last 3 months prior to study enrollment.
• Any prior allogenic or autologous stem-cell transplantation.
• Unresolved toxicity ≥ Grade 2 from previous therapy except for stable chronic toxicities (Grade 2) not expected to resolve, such as stable Grade 2 peripheral neuropathy.
• Prior nonhematologic malignancy except for the following: Malignancy treated with curative intent and with no evidence of active disease for more than 2 years before screening. Adequately treated carcinoma in situ without current evidence of disease.

Other protocol-defined Inclusion/Exclusion Criteria apply.

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.

Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.