Leading in MPNs Beyond Ruxolitinib in Combo With T-Regs

• Safety Run-in

The study will employ a 3+3+3 design to assess the safety and tolerability of the treatment based on treatment-limiting toxicities (TLTs) occurring up to 1 Cycle (28 days) after the first infusion.

• Expansion

After a total of 9 participants completed 28 days and are evaluated for tolerability in the safety run-in phase, additional participants may be included in the expansion cohort in order to have approximately 24 evaluable myelofibrosis

Inclusion criteria

• Ability to comprehend and willingness to sign a written informed consent form (ICF) for the study.
• Age above 18 years inclusive at the time of signing the ICF.
• Participants who fulfill the diagnostic criteria of myelofibrosis including primary myelofibrosis and myelofibrosis arising from polycythemia vera and essential thrombocythemia
• Life expectancy is greater than 6 months.
• Subject has been receiving ruxolitinib therapy, is unlikely to benefit from further ruxolitinib monotherapy in the opinion of the investigator; AND meeting the following criteria: receiving ruxolitinib >3 months prior to enrollment; AND stable dose for 8 weeks before starting therapy with CK0804
• Subject with evidence of evaluable residual burden of disease following ruxolitinib monotherapy treatment, consisting of:

• presence of grade ≥2 anemia or thrombocytopenia or neutropenia, OR
• presence of disease-related symptoms, as determined by a Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN SAF TSS) score of ≥10 points, OR
• documented splenomegaly of at least 5 cm below the costal margin as measured by physical examination or splenomegaly as documented by ultrasound or MRI.
• Willingness to avoid pregnancy or fathering children based on the criteria below

• Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last study treatment dose and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing should be communicated to the participants and their understanding confirmed.
• Women of childbearing potential must have a negative serum pregnancy test at screening before the first dose (within 3 days of the first study treatment dose) and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through the safety follow-up visit and must not donate oocytes during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed,
• Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible.
• ECOG performance status of 0 to 2

Exclusion criteria

• Any major surgery within 28 days before the first dose of study treatment.
• Undergone any prior allogenic or autologous stem cell transplantation or a candidate for such transplantation.
• Received chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody or hypomethylating agent to treat the participant's disease, with the exception of ruxolitinib, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
• Participant has received splenic irradiation within the past 6 months.
• Significant concurrent, uncontrolled medical condition or infections, which in the opinion of the principal investigator may interfere in the study participation.
• Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator.
• Women who are pregnant or breastfeeding.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
• Participants with laboratory values at screening as defined

• Platelets < 50 × 10^9/L without the assistance of growth factors, thrombopoietic factors, or platelet transfusions
• ANC < 0.5 × 10^9/L
• ALT ≥ 2.5 × ULN
• AST ≥ 2.5 × ULN
• Direct Bilirubin > 2.0 × ULN
• ALP ≥ 3 × ULN
• Creatinine clearance < 50 mL/min according to Cockcroft-Gault formula.
• Unwillingness to be transfused with blood components including RBC and platelet transfusions.
• Inability of the participant (or parent, guardian, or legally authorized representative) to comprehend the ICF or unwillingness to sign the ICF.