Study of Select Combinations in Adults With Myelofibrosis

Key inclusion criteria:

1. Signed informed consent must be obtained prior to participation in the study.
2. Male or female subjects must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
3. Subjects have a diagnosis of PMF as defined by the WHO criteria, or diagnosis of PET-MF or PPV-MF as defined by the IWG-MRT criteria (International Working Group for Myelofibrosis Research and Treatment).
4. Subjects must have been treated with a JAK inhibitor for ≥3 months with inadequate efficacy response defined as \<10% spleen volume reduction by MRI or \<30% decrease from baseline in spleen length by physical examination or regrowth to these parameters following an initial response.

   And/or

   Treatment for ≥28 days complicated by either:
   * Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months); or
   * Grade ≥3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while on treatment with JAK inhibitor.
5. Palpable spleen of at least 5 cm from the LCM to the point of greatest splenic protrusion or enlarged spleen volume of at least 450 cm3 per MRI or CT scan at baseline (an MRI/CT scan up to 8 weeks prior to first dose of study treatment can be accepted).
6. Absolute neutrophil count (ANC) ≥ 1000/μL.
7. Dose evaluation / Dose escalataion: Platelet count ≥ 75,000/μL without transfusion support Dose expansion: Platelet count ≥ 50,000/μL without transfusion support.

Key exclusion criteria:

1. Subjects with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), or peripheral blasts ≥ 10 %, or AML transfromed from previous MPN.
2. Subjects having received JAK inhibitors, systemic antineoplastic therapy (including unconjugated therapeutic antibodies, toxin immunoconjugates, and alpha-interferon) or any experimental therapy within 14 days or five half-lives, whichever is shorter, before the first dose of study treatment.
3. Prior autologous or allogeneic stem cell transplant at any time.
4. Candidate for allogenic hematopoietic stem cell transplantation at the time of enrolment.
5. Splenic irradiation within 6 months prior to the first dose of study treatment.
6. Prior splenectomy.