MPN-RC 118 AVID200 in Myelofibrosis

Inclusion Criteria: * Subjects must be ≥18 years of age at the time of signing the Informed Consent Form (ICF) * Subjects must voluntarily sign an ICF * Subjects must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF (note that all diagnoses must include the presence of at least Grade 2 marrow fibrosis according to the European Consensus on Grading of Bone Marrow Fibrosis (see Table 6) with intermediate -2 or high risk disease according to the IWG-MRT Dynamic International Prognostic Scoring System (DIPSS) (see Table 7) * A bone marrow biopsy must be performed within the 30 day screening period, however, a bone marrow biopsy obtained within 90 days of screening without intervening treatments and approved by the study chair may suffice. * Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. * Life expectancy of at least six months * At least two weeks must have elapsed between the last dose of any MF-directed drug treatments (including investigational therapies and excluding hydroxyurea) and study enrollment * Not eligible for ruxolitinib therapy due to a platelet count \<50 x 109/L, previously treated and lack/loss of response as defined by at least one of the following: 1. Treatment 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 2. Treatment for ≥28 days complicated by either i. Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months) ii. National Cancer Institute (NCI) CTCAE grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of \< 20 mg BID * Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia * Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if ≤55 years or 12 months if \>55 years, must have a negative serum pregnancy test at screening and cycle 1 day 1 and must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception include use of oral contraceptives or Depo-Provera, with an additional barrier method (diaphragm with spermicidal gel or condoms with spermicide), double-barrier methods (diaphragm with spermicidal gel and condoms with spermicide), partner vasectomy, and total abstinence. * Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. * Must have adequate organ function as demonstrated by the following: 1. ALT (SGPT) and/or AST (SGOT) ≤ 3x upper limit of normal (ULN), or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis \[EMH\] related to MF); 2. Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to extra-medullary hematopoiesis related to MF or documented Gilbert's syndrome); 3. Serum creatinine ≤ 2.0 mg/dL; 4. Platelet count ≥25 x 109/L * Ability to adhere to the study visit schedule and all protocol requirements * Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: * Other invasive malignancies within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer. * Previous exposure to galunisertib, fresolimumab, sotatercept, or luspatercept. * History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months * Have moderate or severe cardiovascular disease: 1. have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension 2. have documented major ECG abnormalities (not responding to medical treatments) * Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by CT scan/MRI with contrast) * Presence of active serious infection; * Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study * Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection * Organ transplant recipients other than bone marrow transplant * Women who are pregnant or lactating