TrasGEX™: Dose Escalation Study

• To determine preliminary evidence of activity [ Time Frame: approx. every 8 weeks ] [ Designated as safety issue: No ]
  CT or MRI imaging will be performed. Assessment of tumor response (SD, PR, CR. PD) will be performed following a modified version of the revised RECIST guidelines, version 1.1. Basically, patients will receive treatment with TrasGEX™ until progression of disease and/or unacceptable toxicities are observed.
• safety and tolerability of TrasGEX™ [ Time Frame: until 4 weeks after the last treatment with TrasGEX™ ] [ Designated as safety issue: Yes ]
  To assess the safety and tolerability of TrasGEX™ in patients with advanced and/or metastatic HER-2-positive cancer at various dose levels considering observed adverse events, laboratory values, vital signs, ECOG performance status and physical examination.
• To assess the pharmacokinetic (PK) profile of TrasGEX™ (part I) [ Time Frame: prior to 1st infusion until the end of 5th infusion ] [ Designated as safety issue: No ]
  c(max): to determine the PK profile samples will be taken before the first infusion and up to 24 h after after infusion, followed by weekly samples for the first infusion and samples immediately before and after infusion for the following infusions
• To assess the pharmacokinetic (PK) profile of TrasGEX™ (part II) [ Time Frame: prior to 1st infusion until the end of 5th infusion ] [ Designated as safety issue: No ]
  t(1/2): to determine the PK profile samples will be taken before the first infusion and up to 24 h after after infusion, followed by weekly samples for the first infusion and samples immediately before and after infusion for the following infusions

This is a prospective, open label, multicenter study evaluating the safety, tolerability and pharmacokinetics of TrasGEX™ after intravenous administration in patients with HER-2 positive cancers. The effect of TrasGEX™ on the development of anti-drug antibodies and on tumour response will also be evaluated.

Main Inclusion Criteria:

1. Signed written informed consent granted prior to initiation of any study-specific procedures;
2. Male or female patients of ≥18 years of age;
3. ERBB2 (HER-2) gene amplification or ERBB2 overexpression
4. Histologically or cytologically confirmed cancer, either locally advanced or metastatic;
5. No anti-tumor therapy of proven benefit available at study enrollment;
6. Life expectancy of >=3 months;
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) <=2;
8. Male or female patients of child-producing potential must agree to use contraceptive measures or oral contraception during the study and for 28 days after the last dose of TrasGEX™;
9. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of TrasGEX™;

and

Main Exclusion Criteria:

1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks of the first dose of TrasGEX™;
2. Major surgery within four weeks of the first dose of TrasGEX™;
3. Newly diagnosed brain metastases, metastases that have been documented to be stable for <3 months, or metastases for which systemic corticosteroids are required;
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition as TrasGEX™;
5. History of myocardial infarction within 12 months of the administration of the first dose of TrasGEX™;
6. History of congestive heart failure defined as Class II to IV per New York Heart Association classification within 12 months of the administration of the first dose of TrasGEX™;
7. Left ventricular ejection fraction <50%;
8. Previous malignancy other than the current diagnosis within 5 years of the first dose of TrasGEX™;
9. Pregnancy or lactation; and
10. Concurrent uncontrolled significant illness