Safety, Immunogenicity and Pharmacokinetics of SYN004 in Patients With Solid Tumors
Condition: Colon Cancer, Breast Cancer, Cancer of the Head and Neck
MeSH terms: Head and Neck Neoplasms; Breast Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      A first-in-human evaluation of SYN004, a monoclonal antibody that binds to the EGF receptor
      on cancer cells. Cetuximab, a marketed antibody, has been shown to be effective by inhibiting
      the growth of cancer cells thereby prolonging the life of patients who have received it.
      SYN004 is a closely related monoclonal antibody also binds to the EGF receptor in the same
      way. SYN004 might also inhibit cancer cells and prolong life but has been engineered to avoid
      some of the hypersensitivity reactions known to provoked by cetuximab.
    

Detailed description: 
      Study Design:

      In this open-label, dose escalation study, subjects will receive a single IV loading dose of
      SYN004 on Day 1 of the first treatment week, followed by up to 7 fixed weekly doses of
      SYN004. Subjects will be assigned to loading and fixed doses by dose group.

      Each dose group will comprise 3 subjects and may be expanded to 6 subjects. Subjects will
      enter dose groups in the order in which they are enrolled. There will be no intra-subject
      dose adjustments.

      Only 1 subject in a cohort may receive the loading dose of SYN004 on any given day; at least
      1 day must elapse before the next subject in the cohort receives the loading dose.

      Study SYN004-001 Dose Matrix. Three initial subjects will be enrolled followed by an
      additional three if specified by protocol. Dose levels are specified below.

      Group 1: Loading dose: 100 mg/m2; Weekly Dose: 62.5 mg/m2. Group 2: Loading dose: 200 mg/m2;
      Weekly Dose: 125 mg/m2. Group 3: Loading dose: 400 mg/m2; Weekly Dose: 250 mg/m2.

      After each dose of IV SYN004, subjects will be observed in the clinic for 12 hours. After the
      loading dose, subjects will undergo safety evaluations on Days 2, 3 and 5. Safety evaluation
      will also be performed on Day 1 (pre-treatment) and Day 3 of each fixed dose treatment week.

      Dose-limiting toxicities (DLTs) are defined as any Grade ≥3 AE assessed by the investigator
      or Medical Monitor, with agreement of the Safety Review Board (SRB), as related to SYN004.
      Subjects with DLTs will be withdrawn from treatment. If 2 or more subjects in a dose group
      experience DLTs, or one subject in a dose group experiences a Grade ≥3 infusion reaction, all
      subjects in that dose group will be withdrawn from treatment.

      Subjects in the dose groups are considered evaluable for dose escalation decisions if they
      receive at least 4 doses of SYN004, or discontinue SYN004 because of a DLT.

      Subjects who withdraw or are terminated per protocol before receiving 4 doses of SYN004 will
      be replaced.

      For subjects who receive at least 4 doses of SYN004, End of Study CT scans for RECIST
      (version 1.1) evaluation will be performed six (6) days following the final SYN004 treatment.

      There will be a 28-day safety monitoring period following the final dose of SYN004 for all
      subjects in the study. All subjects will attend an End-of-Study Visit 28 days after the final
      dose of SYN004.

      Subjects who complete Cycles 1 and 2, who have evidence of improvement per RECIST 1.1 (i.e.,
      findings of complete or partial response per RECIST 1.1) and meet the other eligibility
      criteria will be offered up to 3 additional treatment cycles (i.e., up to 12 additional
      weekly doses) of SYN004 in the SYN004-001 Extension Study. During the Extension Study,
      subjects will receive the same fixed dose of SYN004 they received in Cycles 1 and 2.

      Dose escalation will proceed according to a standard 3+3 study design.
    

Intervention name(s): SYN004
Intervention type(s): Biological
Intervention description(s): subjects who have received effective treatment for their cancers are eligible
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: SYN004; cetuximab