Japanese Phase 1 Trial of Sym004 in Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Intervention: Sym004
Intervention description: Part-A (dose-escalation): Sym004 will be administered intravenously either weekly at 6 to 12 milligram per kilogram (mg/kg) or biweekly at 18 mg/kg from Week 1 until unacceptable toxicity, disease progression, or consent withdrawal. Part-B (dose-expansion): After the maximum tolerated dose (MTD) is determined in Part-A, up to 30 additional subjects will continue to receive treatment in Part-B.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Solid tumors; Sym004; Phase 1

Summary:

      This trial is to assess the safety and tolerability of Sym004, administered weekly or
      biweekly as monotherapy in Japanese subjects with advanced solid tumors.This study consisted
      of two parts, a dose-escalation part ("Part-A") and a dose-expansion part ("Part-B"). In
      Part-A, Sym004 will be administered weekly or biweekly as monotherapy in Japanese subjects
      with advanced solid tumors. In Part-B, Sym004 will be administered weekly as monotherapy to
      Japanese subjects with advanced esophageal squamous cell carcinoma (ESCC) as dose-expansion.
      A subject will receive Sym004 administration weekly at a dose that will determined to be the
      MTD or a dose that will lower than the MTD and determined to be appropriate with
      recommendation by Safety monitoring committee (SMC). The dose going to used in Part-B will be
      determined after safety confirmation of weekly regimens in Part-A of this trial.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Japanese male or female subjects aged greater than or equal to 20 years at the time of
             informed consent signature

          -  Histologically or cytologically confirmed cancer

          -  Refractory or recurrent advanced late stage solid tumors without available therapeutic
             options which are likely to provide patient benefit (failure and/or intolerance to
             standard anti-cancer therapy)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy of at least 3 months

          -  Written informed consent given before any trial-related activities are carried out

          -  Other protocol defined inclusion criteria could apply

        Exclusion Criteria:

          -  Subjects with symptomatic brain metastases

          -  Subjects who received total resection or irradiation of the target lesion

          -  Received any of the following medications within 4 weeks before the first
             administration of Sym004 at Week 1: cytotoxic or cytostatic anti-cancer therapy,
             antibody therapy, tyrosine kinase inhibitors, and any investigational agent

          -  Received vaccine therapy as anticancer treatment within 12 weeks before the first
             administration of Sym004 at Week 1

          -  Diarrhea of greater than Grade 1 according to National Cancer Institute-Common
             Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 (v4.03)

          -  Skin manifestation of greater than Grade 1 according to NCI-CTCAE (v4.03)

          -  Magnesium of less than 0.9 milligram per deciliter (mg/dL)

          -  Abnormal organ or bone marrow function as defined in the protocol

          -  Received immunosuppressive agents (including systemic corticosteroids used at doses
             above 20 milligram per day (mg/day) of prednisolone or equivalent) within 4 weeks
             before the first administration of Sym004 at Week 1

          -  Active severe infection, any other concurrent disease or medical conditions that are
             deemed to interfere with the conduct of the trial as judged by the Investigator

          -  Known human immunodeficiency virus (HIV) positive, active Hepatitis B or C, or
             uncontrolled allergic conditions or allergy to Sym004 or its components

          -  Clinically significant cardiac disease or concurrent, uncontrolled medical condition

          -  Known previous Grade 3 to 4 infusion-related reactions, according to NCI-CTCAE
             (v4.03), with chimeric monoclonal antibodies

          -  Other protocol defined exclusion criteria could apply