A Study to Evaluate INCA035784 in Participants With Myeloproliferative Neoplasms

• Drug: INCA035784

Inclusion Criteria:

• Age 18 years or older at the time of signing the ICF.
• ECOG performance status of 0 to 1 for the dosethe amount of medication taken escalation (Part 1a) and 0 to 2 for the dose expansion (Part 1b).
• Documented CALR exon-9 mutation.
• Confirmed diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results 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 plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding >450×10⁹/L.
• Resistant, refractory, intolerant, or has lost response to ≥1 prior line of therapy for MF and ≥2 prior lines for ET.
• No prior stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells 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).