• Diagnosis of primary myelofibrosis according to the revised World Health Organization criteria or post-essential thrombocythemia-MF or post-polycythemia vera-MF according to the IWG-MRT criteria

• Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF

• Relapsed/refractory to JAK-inhibitor treatment as defined in either inclusion (i), (ii) or (iii) and not eligible for allogeneic stem cell transplantation (ASCT) at screening:

‣ (i) Treatment with JAK-inhibitor for \>= 6 months duration, including at least 2 months at an optimal dose as assessed by the investigator for that participant and at least one of the following:

• no decrease in spleen volume (\< 10% by MRI or CT) from the start of treatment with JAK-inhibitor

∙ no decrease in spleen size (\< 30% by palpation or length by imaging) from the start of treatment with JAK-inhibitor

∙ no decrease in symptoms (\< 20% by Myelofibrosis Symptom Assessment Form \[MFSAF\] or myeloproliferative neoplasm SAF) from the start of treatment with JAK-inhibitor

∙ a score of at least 15 on TSS assessed using the MFSAF v4.0 during screening.

⁃ (ii) Treatment with JAK-inhibitor treatment for\>= 3 months duration with maximal doses (e.g., 20-25 mg twice daily ruxolitinib) for that participant and no decrease in spleen volume/size or symptoms as defined in inclusion criterion (i \[a, b, or c\]).

⁃ (iii) Following maximum tolerated doses of JAK inhibitor therapy for ≥3 months duration, having documented relapsed disease defined as either

• Increase in spleen volume from time of best response by 25% measured by MRI or CT, or

∙ Increase in spleen size by palpation, CT, or ultrasound

‣ (b.i) For splenomegaly of 5-10 cm at the start of JAK inhibitor treatment, at least 100% increase in palpable spleen size from time of best response;

⁃ (b.ii) For splenomegaly of \> 10 cm at the start of JAK inhibitor treatment, at least 50% increase in palpable spleen size from time of best response;

∙ AND not a candidate for further JAK inhibitor at screening per investigator.

• Measurable splenomegaly demonstrated by a palpable spleen measuring \>= 5 cm below the left costal margin or a spleen volume \>= 450 cm\^3 by MRI or CT

• Active symptoms of MF on the MFSAF v4.0 demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale)

• Hematology laboratory test values within the protocol defined limits

• Biochemical laboratory test values must be within protocol defined limits

• Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2

• Participants should follow protocol defined contraceptives procedures

• A woman of childbearing potential must have a negative serum or urine pregnancy test at screening