TrasGEX™: Phase 1 Study in Cancer Patients

Study Overview
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Brief Summary
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This was 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 was also evaluated.

Detailed Description
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Adult patients with advanced and/or metastatic HER2-positive cancer who were resistant to or for whom there was no standard anti-tumor therapy available at the time of enrollment and who had an estimated life expectancy of at least 3 months were eligible for participation in this study. Patients were to receive the study drug until disease progression (clinical or radiologic), unacceptable toxicity, or any other reason leading to termination of study treatment. Dose-escalation was performed in 3 to 6-patient cohorts.

Official Title
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A Phase I Dose-Escalation and Pharmacokinetic Study of TrasGEX™ in Patients With Locally Advanced or Metastatic HER-2-positive Cancer

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: TrasGEX™


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Signed written informed consent granted prior to initiation of any study-specific procedures; Male or female patients of ≥18 years of age; ERBB2 (HER-2) gene amplification or ERBB2 overexpression Histologically or cytologically confirmed cancer, either locally advanced or metastatic; No anti-tumor therapy of proven benefit available at study enrollment; Life expectancy of >=3 months; Eastern Cooperative Oncology Group (ECOG) performance status (PS) <=2; 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™; 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: Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks of the first dose of TrasGEX™; Major surgery within four weeks of the first dose of TrasGEX™; Newly diagnosed brain metastases, metastases that have been documented to be stable for <3 months, or metastases for which systemic corticosteroids are required; History of allergic reactions attributed to compounds of similar chemical or biologic composition as TrasGEX™; History of myocardial infarction within 12 months of the administration of the first dose of TrasGEX™; 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™; Left ventricular ejection fraction <50%; Previous malignancy other than the current diagnosis within 5 years of the first dose of TrasGEX™; Pregnancy or lactation; and Concurrent uncontrolled significant illness

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TrasGEX<br>A total of 37 patients with advanced HER2-positive carcinomas and progressive disease. | Drug: TrasGEX™<br>* Patients received TrasGEX intravenously every 3 weeks until disease progression in doses of 12-720 mg in a three-plus-three dose escalation design, including an expansion cohort at the highest dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| optimal dose and regimen of TrasGEX™ | The primary objective of this first-in-man study is to determine the optimal dose and regimen of TrasGEX™ in patients with locally advanced or metastatic human epidermal growth factor receptor-2 (HER-2)-positive cancer. The recommended phase II dose needs to have an acceptable safety profile and provides evidence for efficacy based on clinical observations or the pharmacokinetic profile. | up to at least 8 weeks after the first TrasGEX™ administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine preliminary evidence of activity | 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. | approx. every 8 weeks | 
| safety and tolerability of TrasGEX™ | 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. | until 4 weeks after the last treatment with TrasGEX™ | 
| To assess the pharmacokinetic (PK) profile of TrasGEX™ (part I) | 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 | prior to 1st infusion until the end of 5th infusion | 
| To assess the pharmacokinetic (PK) profile of TrasGEX™ (part II) | 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 | prior to 1st infusion until the end of 5th infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced solid cancers, metastatic solid cancers