CetuGEX™: Phase 1 Study in Cancer Patients

Glycotope GmbH41 enrolled

Overview

This was a prospective, open label, multicenter study evaluating the safety, tolerability and pharmacokinetics of CetuGEX™ after intravenous administration in patients with EGFR positive, locally advanced and/or metastatic solid cancers. The effect of CetuGEX™ on the development of anti-drug antibodies and on tumour response was also evaluated.

Male or female patients ≥18 years of age with a histologically confirmed locally advanced and/or metastatic solid organ tumor. Patients enrolled in Germany were required to have a positive EGFR overexpression status. Patients must have experienced a failure or non-availability of standard therapy (had received at least one line of chemotherapy and further standard therapy was not an option at study entry). Open-label, non-randomized, inter-patient dose-escalation, multi-center study. Patients were to receive CetuGEX until disease progression or until intolerable toxicities occurred.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumors

Interventions

CetuGEX™DRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female and age ≥ 18 yrs 2. Histologically confirmed EGFR positive locally advanced and/or metastatic solid organ tumour 3. Measurable or non-measurable tumour 4. Failure of standard therapy or non-availability of standard therapy (Patients must have received at least 1 line of chemotherapy and further standard therapy is not an option at study entry) 5. All anti-tumour therapies must be completed 4 weeks before start of study treatment; treatment with Cetuximab must be completed at least 6 weeks prior to study start 6. ECOG Performance Status ≤1 and estimated life expectancy of ≥ 3 months 7. Adequate organ function: * Bone marrow function: hemoglobin ≥ 100 g/L; white blood cell count (WBC) ≥ 3.0 x 10\^9/L; absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L; platelet count ≥ 100 x 10\^9/L * Hepatic: aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 2.5 times upper limit of normal (ULN) (≤ 5 x ULN if hepatic metastases present); bilirubin ≤ 1.5 x ULN; alkaline phosphatase ≤ 5.0 x upper limit of normal (ULN) * Renal: creatinine \< 1.5 x ULN 8. Patients of both genders with procreative potential must use effective contraception while enrolled in the study and for at least 4 weeks after the last study drug infusion 9. Written informed consent must be obtained prior to conducting any study-specific procedures For Expansion Phase only: 10. No prior treatment with Cetuximab allowed Exclusion Criteria: 1. Chemotherapy, radiation, other anti-cancer therapies including any investigational agents at the study enrolment within 4 weeks prior to study enrolment 2. Concurrent anti-tumour therapy or concurrent immunotherapy 3. Concurrent systemic steroids except topical (inhaled, topical, nasal) or replacement therapy for the last 28 days. 4. Major surgery within 4 weeks prior entering the study and/or incomplete recovery from surgery or planned major surgery 5. Primary or secondary immune deficiency 6. Clinically active infections \> CTCAE grade 2 7. Prior allergic reaction to a monoclonal antibody (e.g. Trastuzumab, Cetuximab or Bevacizumab). 8. Active hepatitis B assessed by serology, hepatitis C by histology; human immunodeficiency virus (HIV) seropositivity 9. Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for ≥ 3 years will be allowed to enter the study. 10. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug including unstable diabetes mellitus, vena-cava-syndrome, chronic symptomatic respiratory disease. 11. Clinical signs of brain metastasis or leptomeningeal involvement 12. Symptomatic congestive heart failure (New York Heart Association \[NYHA\] 3 or 4); unstable angina pectoris within 6 months prior to enrollment; significant cardiac arrhythmia, or history of stroke or transient ischemic attack within 1 year. 13. Active drug abuse or chronic alcoholism 14. Pregnancy or Breastfeeding

Locations (5)

Glycotope Investigational Site

Hamburg, Germany

Glycotope Investigational Site

Heidelberg, Germany

Glycotope Investigational Site

Milan, Italy

Glycotope Investigational Site

Milan, Italy

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events (TEAE) assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0

TEAE were coded by use of Medical Dictionary for Regulatory Activities (MedDRA) version 13.1

Time frame: throughout the study until 28±2 days after last infusion

Incidence of clinically relevant abnormal clinical laboratory parameters

graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0

Time frame: from first infusion until 28±2 days following the last infusion

Dose-limiting toxicities (DLT)

DLTs were defined as drug-related: * Hematological or non-hematological toxicity grade 3 (excl. rash) or 4 excluding inadequately treated nausea and vomiting; * In case of skin reaction (rash) grade 4

Time frame: from first infusion until 28±2 days following the last infusion

Changes of corrected QT interval (QTc) duration

by use of 12-lead electrocardiograms (ECG)

Time frame: from first infusion until 28±2 days following the last infusion

To define the recommended phase II dose and regimen

Defining a recommended dose for a Phase II study was possible based on the available PK data in combination with the safety and activity data for CetuGEX™

Time frame: from first infusion until 28±2 days following the last infusion

Secondary Outcomes

Anti-Tumor Activity: Confirmed Best Overall Response Rates

Assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Tumors were measured by computed tomography (CT) scan or magnetic resonance imaging (MRI)

Data from ClinicalTrials.gov

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