Study of Luspatercept for the Treatment of Anemia in Patients With Myelodysplastic Syndrome (MDS) (MK-6143-001)

Key Inclusion Criteria

• Documented diagnosis of idiopathic/de novo myelodysplastic syndrome (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML), according to WHO criteria (white blood count, 13,000/uL), that meets International Prognostic Scoring System (IPSS) classification of low or intermediate-1 risk disease as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC) obtained during screening
• Anemia defined as:
• Mean hemoglobin concentration 500 U/L, OR, if ≤500 U/L, patient is non-responsive, refractory, or intolerant to erythropoiesis-stimulating agents (ESAs), or ESAs are contraindicated or unavailable
• Expansion cohort 2 patients: If patient is RS+ (defined as having ≥15% ring sideroblasts in the bone marrow), no prior ESA treatment and serum erythropoietin level ≤ 200 U/L. If a patient is RS- (defined as having <15% ring sideroblasts in the bone marrow), prior ESA treatment and any serum erythropoietin level is allowed
• No alternative treatment options, per applicable MDS guidelines, are available and/or appropriate for the patient, at the discretion of the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia).
• Adequate renal (creatinine ≤2 x upper limit of normal [ULN]) and hepatic (total bilirubin <2 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 x ULN) function
• Adequate transferrin saturation (≥15%), ferritin (≥ 50 µg/L), folate (≥4.5 nmol/L [≥2.0 µg/L]) and vitamin B12 (≥148 pmol/L [≥ 200 pg/mL]) during screening (supplementation and retest during screening is acceptable)
• Females of child bearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy, or are not naturally postmenopausal ≥24 consecutive months) must have negative urine or blood pregnancy test prior to enrollment and use adequate birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 12 weeks following the last dose of luspatercept. Males must agree to use a latex condom during any sexual contact with females of child-bearing potential while participating in the study and for 12 weeks following the last dose of luspatercept, even if he has undergone a successful vasectomy. Patients must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of luspatercept
• Patients are able to adhere to the study visit schedule, understand and comply with all protocol requirements
• Patients understand and are able to provide written informed consent

Key Exclusion Criteria

• Prior treatment with azacitidine or decitabine
• Treatment within 28 days prior to Cycle 1 Day 1 with:
• Erythropoiesis stimulating agent (ESA)
• Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF)
• Lenalidomide
• Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1
• Treatment with another investigational drug or device, or approved therapy for investigational use ≤28 days prior to Cycle 1 Day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer
• Major surgery within 28 days prior to Cycle 1 Day 1. Patients must have completely recovered from any previous surgery prior to Cycle 1 Day 1
• Platelet count <30 x 109/L.
• Any active infection requiring parenteral antibiotic therapy within 28 days prior to Cycle 1 Day 1 or oral antibiotics within 14 days of Cycle 1 Day 1
• History of stroke, deep venous thrombosis (DVT) or arterial embolism within 6 months prior to Cycle 1 Day 1
• Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV)
• Any malignancy other than MDS which has not been