A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0639 in Advanced Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Intervention: MEDI0639
Intervention description: MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Cancer

Summary:

      This is a first-time-in-human, Phase 1, multicenter, open-label, single-arm, dose-escalation
      (3+3) study to evaluate the safety, tolerability, antitumor activity, PK and immunogenicity
      of MEDI0639.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed solid tumors that are refractory to standard
             therapy or for which no standard therapy exist

          -  Age ≥ 18 years

          -  ECOG Performance Status of 0 or 1

          -  LVEF (measured by Echocardiogram) > 50%

          -  No gastrointestinal bleeding within 1 year of study entry.

          -  Adequate organ and marrow function:

               -  Hemoglobin ≥ 10g/dL

               -  Absolute Neutrophil Count ≥ 1500/mm3

               -  Platelet Count ≥ 100,000/mm3

               -  AST & ALT ≤ 2.5 x ULN

               -  Bilirubin ≤ 1.5 x ULN

               -  Cr Cl ≥ 50 mL/min (as determined by the Cockcroft-Gault equation or by 24-hour
                  urine collection)

          -  Prior therapy against VEGF or VEGFRs including, but not limited to bevacizumab,
             sunitinib, sorafenib, pazopanib, motesanib (AMG706), or cediranib (AZD2171), is
             permitted so long as the agent does not have any known activity against DLL4 and the
             last dose received s at least 6 weeks prior to first dose of MEDI0639.

          -  Life expectancy ≥ 12 weeks

          -  Females of childbearing potential must be surgically sterile, have a sterile male
             partner, be premenarchal or at least 2 years postmenopausal, practice abstinence or
             otherwise must use 2 effective methods of contraception from the time of initiation of
             investigational product.

          -  Males, unless surgically sterile, must use 2 effective methods of contraception with a
             female partner and must agree to continue using such contraception for 90 days after
             the last dose of MEDI0639

        Exclusion Criteria:

          -  Concurrent enrollment in another investigational clinical study

          -  Receipt of any investigational anticancer therapy within 4 weeks prior to the first
             dose of MEDI0639 or in the case of monoclonal antibodies, 6 weeks prior to the first
             dose of MEDI0639

          -  Concurrent or previous treatment with inhibitors of DLL4

          -  Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy
             for cancer treatment

          -  Known bleeding diathesis, esophageal varices, or angioplasty

          -  Pulmonary hemorrhage or gross hemoptysis within 12 months

          -  Known arterial or venous thrombosis or pulmonary embolism within 2 years

          -  Concurrent use of systemic low molecular weight heparin or low dose warfarin

          -  Presence of brain metastases

          -  Cerebrovascular accident or transient ischemic attack within 2 years

          -  Cardiovascular events, such as myocardial infarction, unstable/severe angina,
             coronary/peripheral artery bypass graft, unstable cardiac arrhythmia requiring
             medication, congestive heart failure (NYHA > class II), within 2 years

          -  Tumors with squamous cell histology

          -  Major surgical procedure within 90 days

          -  Pregnancy or lactation

          -  Known HIV positive or Hepatitis A, B, or C infection