A Study of DKN-01 in Multiple Myeloma or Advanced Solid Tumors
Condition: Multiple Myeloma; Solid Tumors; Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: DKN-01
Intervention description: DKN-01 will be administered intravenously (IV) once a week over 30 minutes (min) and 2 hours (max) for 75, 150 and 300 mg. At 600 mg, DKN-01 will be administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: 3 participants will be treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation will occur sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching maximum tolerated dose (MTD) are met (or highest planned dose study group is completed). Cycle 1 will define the dose limiting toxicity (DLT) that governs dose escalation. PART B - Dose Confirmation: Once the MTD is established (or the highest planned dose level), 300 mg of DKN-01 will be administered IV on days 1 and 15 of every 28 day cycle.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: Cancer; Oncology

Summary:

      The purpose of this trial is to characterize the safety and toxicity of DKN-01 by determining
      a maximum-tolerated dose and associated dose limiting toxicity. To evaluate the
      pharmacodynamic response in patients with cancer. To characterize the pharmacokinetic
      parameters of DKN-01 in cancer patients who are intolerant to standard/approved therapies.
    

Eligibility criteria:

        Inclusion Criteria:

        Part A: Patients with histological or cytological confirmed multiple myeloma or advanced
        solid tumors. For multiple myeloma, 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 without elevations they must have measurable increased
        concentrations of free light chains

        Part B: Patients with previously treated, histologically confirmed advanced NSCLC with
        progressive disease requiring therapy

        Parts A and B:

          -  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 Response Evaluation Criteria in Solid Tumors
             (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, if 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

          -  Females with child bearing potential must have a negative serum pregnancy test within
             7 days of study entry

          -  Acceptable liver function, renal function, hematologic status

          -  Urinalysis - No clinically significant abnormalities

          -  Acceptable coagulation status:

               -  Prothrombin Time/Partial Thromboplastin Time (PT/PTT) ≤ 1.2 x upper limit of
                  normal (ULN) (unless receiving anticoagulation therapy - eligibility based upon
                  INR)

               -  International Normalization Ratio (INR) ≤ 1.6 (unless receiving anticoagulant
                  therapy)

                    -  Receiving warfarin; INR ≤ 3.0 and no active bleeding

          -  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

          -  Available for the study duration and willing to follow procedures

          -  Serum calcium:

               -  Solid tumors only: within normal limits

               -  Multiple myeloma: ≤ 11.5 milligrams per deciliter (mg/dL)

        Exclusion Criteria:

          -  History of osteonecrosis of the hip or evidence of structural bone abnormalities in
             the proximal femur on magnetic resonance imaging (MRI) scan considered clinically
             significant or may impact the interpretation of the scan. Degenerative changes of the
             hip joint are not exclusionary

          -  Unable to tolerate the confinement/noise of an MRI scanner or have any
             contraindication for MRI

          -  New York Heart Association Class 3 or 4, cardiac disease, myocardial infarction,
             unstable arrhythmia, or evidence of ischemia

          -  Have Fridericia-corrected QT interval (QTcF) > 470 millisecond (msec) (female) or >
             450 (male), or history of congenital long QT syndrome.

          -  Active, uncontrolled bacterial, viral, or fungal infections

          -  Pregnant or nursing women

          -  Radiation therapy, surgery, or chemotherapy, within 1 month prior to study entry

          -  Previously treated with an anti-Dickkopf-related protein 1 (DKK-1) therapy

          -  Significant allergy to a biological pharmaceutical therapy

          -  History of major organ transplant

          -  Had an autologous or allogenic bone marrow transplant, current acute leukemia, colon,
             prostate, breast or small cell lung cancer, osteoblastic lesions, concomitant disease
             known to influence calcium metabolism including hyperparathyroidism, hyperthyroidism
             and/or Paget's disease of bone

          -  Unwillingness / inability to comply with procedures

          -  Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C

          -  Serious nonmalignant disease

          -  Receiving other investigational agent or have received other investigational agent
             within last 30 days or 5 half-lives, whichever is longer

          -  Receiving lithium chloride (LiCl)