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

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.

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.