A Study to Evaluate INCA035784 in Participants With Myeloproliferative Neoplasms

Inclusion Criteria:

* Age 18 years or older at the time of signing the ICF
* ECOG performance status of 0 to 1 for the dose escalation (Part 1a) and 0 to 2 for the dose expansion (Part 1b)
* Documented CALR exon-9 mutation
* Confirmed diagnosis of MPN according to the 2022 ICC criteria:

  * DIPSS+ intermediate-2/high-risk MF with prior JAKi, \<20% blasts, and measurable spleen
  * High-risk ET with platelets \>450×10⁹/L
* Resistant, refractory, intolerant, or has lost response to ≥1 prior line of therapy for MF and ≥2 prior lines for ET (unless only a single standard-of-care option is approved in the participating country)
* No prior stem cell transplant and none planned within 6 months
* Minimum Laboratory Requirements:

  * Platelet count ≥50 × 10⁹/L
  * Absolute neutrophil count ≥1 × 10⁹/L
  * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN), unless receiving vitamin K antagonists
  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 × ULN
  * Total bilirubin \<2 × ULN
  * Estimated creatinine clearance \>45 or \>30 mL/min (depending on study part)

Exclusion Criteria:

* Major bleeding or thrombosis (e.g., stroke, DVT, PE) within the past 3 months
* Active or high-risk HBV, HCV, or HIV infection, or other chronic active infections requiring systemic treatment
* Active invasive cancer within the past 2 years, except certain early-stage or low-risk cancers (e.g., resected skin, cervical, thyroid, or prostate cancer)
* Pregnant or unwilling to avoid pregnancy or fathering a child during the study and for a defined period after the last dose.

Other protocol-defined Inclusion/Exclusion Criteria may apply.