A Phase 1 Study of LY5830966 in Participants With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i)

Prior treatment

• Prior splenectomy or splenic irradiation within 3 months.
• Ongoing use of systemic corticosteroids at dose equivalent to greater than (\>) 20 milligrams per day (mg/day) of prednisone.
• Chemotherapy in the previous 4 weeks or prior JAK2 inhibitor not discontinued per required washout prior to first dose
• Requirement for therapy with a medication that is a strong Cytochrome P450 3A4 CYP3A4 inhibitor as a concomitant medication.
• Currently on an interventional therapeutic trial in the treatment phase.
• Prior treatment with JAK2 inhibitors
  • High-risk R/R PV only:
• Prior PV-directed therapy without required washout
• Active or chronic bleeding within 2 months prior to enrollment
• Clinically significant thrombosis (e.g., pulmonary embolism, deep vein thrombosis, or splenic vein thrombosis) within 2 months prior to enrollment

Other illness

• Active, uncontrolled systemic infection or active Hepatitis B or C
• Significant cardiovascular disease
• Active second primary malignancy (or diagnosed within 2 years) at high risk of progression, with standard exceptions (treated skin cancer, in situ cervical cancer, curatively treated localized breast/prostate cancer)
• Individual with a history of (noninfectious) pneumonitis/interstitial lung disease.
  • First line (1L) MF only:

Other

• Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v 5.0).
• Pregnant or breastfeeding: males planning to father a child during treatment and for 3 months after last dose.
• Prolongation of the corrected QTcF ≥470 millisecond during screening
• Requires phlebotomy at hematocrit levels \<45%.

• Diagnosis of PMF, post-PV MF, or post-ET MF.
• Dynamic International Prognostic Scoring System (DIPSS) Intermediate-1, Intermediate-2 or High-risk MF with less than or equal to (≤)10% blasts, regardless of JAK2 mutation status.
• Estimated spleen volume greater than or equal to (≥)450 cubic centimeter (cm ³)
• Myelofibrosis Symptom Assessment Form, version 4.0 (MFSAF v.4.0) TSS ≥10, or at least 2 of 7 MFSAF-assessed symptoms with scores ≥3.
• Eastern Cooperative Oncology Group performance score (ECOG PS) of 0, 1, 2, or 3.
• Prior therapy with at least 1 type I JAK2 inhibitor, and either failed to achieve a response or relapsed after achieving a response.
• Absolute neutrophil count greater than or equal to 1,000 per microliter of blood (ANC ≥1.0×10\^9/L).
• Platelet count ≥75×10\^9/L.
• Estimated glomerular filtration rate greater than or equal to 45 milliliters per minute per 1.73 square meters (eGFR ≥45 mL/min/1.73m²).
• Serum total bilirubin ≤2.0 × upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × upper limit normal (ULN).
• QTcF ≤470 msec.
  • Polycythemia vera (PV) Only
• Confirmed diagnosis of PV
• Participants must have high-risk disease as defined by 60 years of age or older and/or have prior history of thrombotic event
• R/R or intolerant to at least one line of prior therapy including but not limited to interferon-based therapies, ruxolitinib, or hydroxyurea (HU) as defined by European LeukemiaNet (ELN) criteria