Clinical Study of CWP232291 in Relapsed or Refractory Myeloma Patients

Inclusion criteria

• Able to understand and then sign an informed consent form (ICF) prior to initiation of any study-specific procedure and treatment.
• ≥ 18 years of age.
• Confirmed measurable MM based on the following:

• Serum M component (≥ 0.5 g/dL), or
• Urine M protein ≥ 200 mg/24 hours), or
• Serum immunoglobulin free light chains ≥ 10 mg/dL and abnormal serum immunoglobulin kappa/lambda free light chain ratio), or
• Non-secretory disease measurable with bone marrow biopsy or radiography.
• Failed 2 or more prior standard MM therapies, and >100 days post autologous bone marrow transplant prior to first dose for transplanted subjects. Prior lenalidomide is permitted.
• In the absence of rapidly progressing disease, the interval from prior treatment to time of study drug administration should be ≥ 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. Persistent clinically significant toxicities from prior chemotherapy or radiotherapy must not be greater than Grade 1.
• Eastern Cooperative Oncology Group (ECOG) performance score 0-2 (Appendix 3).
• Adequate bone marrow function:

• Absolute neutrophil count (ANC) ≥ 1000/mm3, independent of growth factor support;
• Platelet count ≥ 75,000/mm3;
• Hb ≥ 9 g/dL (independent of transfusions or erythropoiesis-stimulating agents [ESA]).
• Adequate renal function:

• Serum creatinine ≤ 2.5 mg/dL;
• Creatinine clearance (CrCl) ≥ 60 mL/minute (Cockcroft-Gault).
• Adequate hepatic function:

• Total bilirubin < 2.5 x upper limit of normal (ULN); direct bilirubin < 2 x ULN for Gilbert's syndrome;
• Alkaline phosphatase (AP) ≤ 2.5 x ULN, unless considered due to organ leukemic involvement;
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x ULN.

• Women of child-bearing potential (ie, women who are premenopausal or not surgically sterile):

• Two effective forms of contraception (abstinence, intrauterine device, oral contraceptive, or double barrier device) from the time of informed consent and until at least 4 weeks after discontinuing study drugs, and
• Negative serum or urine pregnancy tests during screening and then within 3 days prior to Day 1. 12. Sexually active men - effective contraceptive methods in subject and partner from the time of informed consent and until ≥ 4 weeks after discontinuing study drugs. 13. Able to adhere to the study visit schedule and other protocol requirements.

Exclusion criteria

• Chemotherapy or immunotherapy < 5 half-lives prior to screening.
• Not recovered to Grade 1 from adverse effects of prior myeloma therapy or radiotherapy prior to screening.
• Systemic corticosteroids < 1 week prior to Day 1 in Phase 1a. Subjects may receive stable physiologic replacement doses of glucocorticoids (up to the equivalent of 10 mg daily prednisone) as maintenance therapy for adrenal insufficiency.
• Uncontrolled intercurrent illness including infections and psychiatric illness/social situations that may limit compliance with protocol requirements or the evaluation of study drugs.
• Active cardiovascular disease including myocardial infarction (MI) < 6 months of screening, symptomatic coronary artery disease (CAD), arrhythmias, hypertension, or heart failure not controlled by medication.
• History of deep venous thrombosis and pulmonary embolism (Phase 1b).
• Anticoagulants < 7 days prior to Day 1. Aspirin is permitted in Phase 1b per standard of care with lenalidomide-based therapy.
• Active central nervous system (CNS) disease.
• Known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C.
• Pregnant or nursing women.
• History of hypersensitivity to lenalidomide (Part B only)
• History of other active malignancies < 3 years prior to screening except basal cell carcinoma, low grade Gleason score ≤ 6 prostate cancer that has been removed with undetectable prostate-specific antigen (PSA), and in situ cervical carcinoma.