Study of ACE-011 to Determine Safe and Effective Dose of ACE-011 for the Treatment of Chemotherapy Induced Anemia in Patients With Advanced Non-small Cell Lung Cancer

Inclusion Criteria:

1. Men and women > 18 years of age

2. Part 1: Histologically confirmed (cytology or biopsy) solid tumor malignancy, excluding those solid tumors treated with curative intent.

   Part 2: Histologically confirmed non-small cell lung cancer

3. Documented metastatic disease
4. Measurable or non-measurable disease evaluable by Response Evaluation Criteria in Solid Tumors (RECIST)

5. All of the following laboratory values:

   • Hemoglobin ≥ 6.5 to < 11.0 g/dL (≥ 65 to < 110 g/L), due to chemotherapy-induced anemia
   • Absolute neutrophil count ≥ 500/mm3
   • Platelet count ≥ 75,000/mm3 (> 72 hours since prior platelet transfusion

   • Adequate renal function

     • creatinine clearance ≥ 40mL/min or ≥ 50 mL/min if cisplatin is concomitantly administered and
     • urine protein / creatinine ratio ≤ 1.0; or ≤ 2.0 if bevacizumab (Avastin®) is concomitantly administered
   • Hepatic function (bilirubin < 1.5 x ULN; AST and ALT < 3.0 x ULN and ≤ 5.0 ULN for subjects with liver metastases)

6. Subjects must have received:

   • at least one cycle and up to 4 cycles (q3w schedule) of platinum-based chemotherapy and be randomized prior to receiving Cycle 5 OR
   • at least one cycle and up to 3 months (depending upon regimen) of platinum-based chemotherapy
7. >28 days since previous treatment with ESA
8. >14 days since last red blood cell transfusions
9. Eastern Oncology Cooperative Group (ECOG) Performance status 0-2
10. For females of childbearing potential, highly effective method of birth control for at least 28 days before starting study, during participation and at least 112 days following last dose of ACE-011
11. Males must use latex condom or non-latex condom not made of (animal) membrane during any sexual contact with female of childbearing potential
12. Life expectancy of >3 months
13. Willing to adhere to study visit schedule
14. Understand and voluntarily sign informed consent

Exclusion Criteria:

Part 2 only, history of prior regimen(s)of platinum-based chemotherapy for metastatic NSCLC and/or history of adjuvant platinum-based chemotherapy with last dose received less than six months prior to the start of current first-line platinum-based chemotherapy for metastatic NSCLC.

1. National Cancer Institute Common Terminology for Adverse Events Grade >3 toxicity
2. Prior radiation to >20% of whole skeleton
3. Prior regimen(s) of platinum based chemotherapy for metastatic disease and/or history of adjuvant platinum-based chemotherapy with the last dose received less than six months prior to the start of current first-line platinum-based chemotherapy for metastatic disease
4. Central nervous system metastases
5. Clinically significant pulmonary, endocrine, neurologic, gastrointestinal, hepatic, or genitourinary disease unrelated to underlying malignancy
6. Classification of 3 or higher heart failure (as classified by New York Heart Association)
7. History of thrombosis, deep vein thrombosis, pulmonary emboli, or embolic stroke, if not stable on anticoagulants and/or one of these events occurring in past 6 months
8. Diagnosis of a myeloid malignancy or known history of myelodysplasia
9. Recent history (within 14 days of Day 1) of IV/oral antibiotics due to post septic episode
10. Uncontrolled hypertension. Controlled hypertension is considered clinically stable, and systolic blood pressure (SBP) must be < 150 mmHg and diastolic blood pressure (DBP) must be < 100 mmHg.
11. Known human immunodeficiency virus (HIV)
12. Known active hepatitis B or C antibody
13. Iron deficiency
14. History of anemia as a result of inherited hemoglobinopathy
15. History of anemia due to autoimmune or hereditary hemolysis or gastrointestinal bleeding
16. Received treatment with another investigational drug or device within 28 days prior to Day 1, or if the half life of the previous product is known, within 5 times the half life prior to dosing, whichever may be longer.
17. Any prior use of Sotatercept (ACE-011).
18. Pregnant or lactating females or females planning to become pregnant
19. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (Refer to the Investigator's Brochure for further information).
20. Major surgery within 30 days prior to Day 1 (subjects must have completely recovered from any previous surgery prior to Day 1).