A Study of DKN-01 in Multiple Myeloma or Advanced Solid Tumors

Inclusion Criteria:

• Part A Only: Patients with histological or cytological confirmed multiple myeloma or advanced solid tumors. For multiple myeloma, patients must have symptomatic myeloma as defined by the International Myeloma Working Group inclusive of measurable serum and/or urine monoclonal protein (M-protein) or for those patients without elevations they must have measurable increased concentrations of free light chains
• Part B Only: Patients with previously treated, histologically confirmed advanced NSCLC with progressive disease requiring therapy
• Parts A and B as follows:
• Patients must be refractory or intolerant to all standard/approved therapy(ies)
• Patients with solid tumors must have one or more metastatic tumors measurable on computed tomography (CT) scan using RECIST criteria
• Radiation for symptomatic lesions outside the central nervous system (CNS) must have been completed at least 2 week prior to study enrollment
• Treated brain metastases will be allowed, provided they are asymptomatic. Patients must be off corticosteroids for at least 2 week prior to study entry
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1
• Life expectancy of at least 3 months
• Ambulatory patients greater than or equal to (≥) 30 years of age
• Signed, Institutional Review Board (IRB) - approved informed consent
• Females with child bearing potential must have had a negative serum pregnancy test within 7 days of study entry

• Acceptable liver function:

  • Bilirubin less than or equal to (≤) 1.5 times upper limit of normal Aspartate transaminase (AST) serum glutamic-oxaloacetic transaminase (SGOT), alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase ≤ 2.5 times upper limit of normal (if liver metastases are present, then ≤ 5 times the upper limit of normal (ULN) is allowed)

• Acceptable renal function:

  • Solid tumor patients: Serum creatinine within normal limits, and/or calculated creatinine clearance greater than or equal to (≥) 60 milliliters/per minute (mL/min) using the Cockcroft and Gault Method
  • Multiple myeloma patients: Serum creatinine ≤ 1.5 x ULN and/or a calculated creatinine clearance ≥ 45 mL/min using the Cockcroft and Gault Method

• Acceptable hematologic status:

  • Granulocyte ≥ 1500 cells/cubic millimeter (cells/mm3)
  • Hemoglobin ≥ 9 grams per deciliter (g/dL)

  • Platelet counts:

    • Solid tumor patients ≥ 100,000 (plt/mm3)
    • Multiple myeloma patients ≥ 75,000 (plt/mm3)

• Urinalysis:

  • No clinically significant abnormalities

• Acceptable coagulation status:

  • Prothrombin Time/Partial Thromboplastin Time (PT/PTT) ≤ 1.2 x ULN

  • International Normalization Ratio (INR) ≤ 1.6 (unless receiving anticoagulant therapy)

    • If receiving warfarin; INR ≤ 3.0 and no active bleeding (that is, no bleeding within 14 days prior to first dose of study therapy)

• For men and women of child-producing potential, the use of effective contraceptive methods during the study and for women 18 months following the last dose of study drug

  • NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) during the study, and women must agree to use adequate contraception prior to study entry and for 18 months after their last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

• Serum calcium:

  • For solid tumors only: within institutional normal limits
  • Multiple myeloma: ≤ 11.5 milligrams per deciliter (mg/dL)

Exclusion Criteria:

• History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on magnetic resonance imaging (MRI) scan that are considered clinically significant or may have an impact on the interpretation of the scan. Degenerative changes of the hip joint are not exclusionary

• Are unable to tolerate the confinement/noise of an MRI scanner or have any contraindication for MRI, including but not limited to the following:

  • Cardiac pacemakers
  • Prosthetic heart valves
  • Metallic splinters in the eye
  • Ferromagnetic hemostatic clips in the central nervous system or body hemostatic clips
  • Cochlear implants
  • Adhesive transdermal patch, if not removed before scans
• New York Heart Association Class 3 or 4, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on echocardiogram (ECG)
• Have Fridericia-corrected QT interval (QTcF) greater than (>) 470 millisecond (msec) (female) or > 450 (male), or history of congenital long QT syndrome. Any ECG abnormality that in the opinion of the investigator would preclude safe participation in the study
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Pregnant or nursing women
• Treatment with radiation therapy, surgery, or chemotherapy, within 1 month prior to study entry (6 week for nitrosoureas or Mitomycin C)
• Previously treated with an anti-DKK-1 therapy
• Significant allergy to a biological pharmaceutical therapy that, in the opinion of the investigator, poses an increased risk to the patient
• History of major organ transplant (for example: heart, lungs, liver and kidney)
• Have had an autologous or allogenic bone marrow transplant
• Have current acute leukemia
• Patients diagnosed with colon, prostate, breast or small cell lung cancer
• Have osteoblastic lesions
• Have concomitant disease known to influence calcium metabolism including hyperparathyroidism, hyperthyroidism and/or Paget's disease of bone
• Unwillingness or inability to comply with procedures required in this protocol
• Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Serious nonmalignant disease (for example: hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
• Patients who are currently receiving any other investigational agent or have received an investigational agent within last 30 days or 5 half-lives, whichever is longer
• Patients who are currently receiving lithium chloride (LiCl)