Study of Subcutaneously Administered Peginesatide in Anemic Cancer Patients Receiving Chemotherapy

This was a Phase 2, open-label, multi-center, sequential dose finding study with up to 6 treatment cohorts receiving chemotherapy with 15 participants per cohort. The primary objective of this study was to determine the dose of peginesatide administered every 3 weeks (Q3W) by subcutaneous injection associated with a hemoglobin increase of ≥ 1 g/dL in ≥ 50% of anemic cancer participants receiving chemotherapy at 9 weeks following the first dose.

Inclusion criteria

• Participant is informed of the investigational nature of this study and has given written, witnessed informed consent in accordance with institutional, local, and national guidelines
• Males or females ≥ 18 and ≤ 80 years of age; pre-menopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening; those who are sexually active must practice a highly effective method of birth control for at least 2 weeks prior to study start, and must be willing to continue practicing birth control for at least 4 weeks after the last dose of study drug. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence (only acceptable if practiced as a life-style and not acceptable if one who is sexually active practices abstinence only for the duration of study) or vasectomized partner
• Participants with histologically confirmed solid tumor malignancy or lymphoma who are scheduled to receive at least 9 weeks of cyclic myelosuppressive chemotherapy while on study
• Hemoglobin value of ≥ 8 and < 11 g/dL within 1 week prior to administration of study drug.
• ECOG Performance Status of 0-2
• One reticulocyte hemoglobin content (CHr) > 29 picograms within 4 weeks prior to study drug administration.
• One transferrin saturation ≥ 15% within 4 weeks prior to study drug administration.
• One serum or red cell folate level above the lower limit of normal within 4 weeks prior to study drug administration
• One vitamin B12 level above the lower limit of normal within 4 weeks prior to study drug administration
• One absolute neutrophil count ≥ 1.0 x 10^9/L within 1 week prior to administration of study drug
• One platelet count ≥ 75 x 10^9/L within 1 week prior to administration of study drug
• Life expectancy > 6 months.

Exclusion criteria

• Treatment with any erythropoiesis stimulating agent (ESA) in the past 90 days
• History of failure to respond to ESA treatment
• Known antibodies to other ESAs or history of pure red cell aplasia (PRCA)
• Acute or chronic leukemia, myelodysplastic syndrome (MDS), or multiple myeloma
• Any previous or planned radiotherapy to more than 50% of either the pelvis or spine
• Known intolerance to parenteral iron supplementation
• Red blood cell transfusion within 4 weeks prior to study drug administration
• Known hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all types, etc.)
• Known hemolysis
• History of pulmonary embolism or deep venous thrombosis (DVT) in the previous 2 years or current therapeutic doses of anticoagulants
• Known blood loss as a cause of anemia
• Uncontrolled, or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal; AST or ALT > 5 times the upper limit of normal if liver metastases are present.
• Creatinine > 175 micromoles per liter (µmol/L)
• History of bone marrow or peripheral blood cell transplantation
• Pyrexia/fever of ≥ 39 °C within 48 hours prior to study drug administration
• Poorly controlled hypertension, per the Investigator's judgment, within 4 weeks prior to study drug administration (e.g., systolic ≥ 170 mm Hg or diastolic ≥ 100 mm Hg on repeat readings)
• Epileptic seizure in the 6 months prior to study drug administration
• Advanced chronic congestive heart failure - New York Heart Association Class IV
• High likelihood of early withdrawal or interruption of the study
• Anticipated elective surgery during the study period
• History of multiple drug allergies
• Exposure to any investigational agent within 1 month prior to administration of study drug or planned receipt during the study period.