CetuGEX™: Phase 1 Study in Cancer Patients

Dose-escalation, PK- and Safety Study With Single Agent CetuGEX™ in Patients With EGFR Positive Locally Advanced and/or Metastatic Cancer

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: CetuGEX™

Detailed Description

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
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, D-20246
    • Glycotope Investigational Site
  • Heidelberg, Germany, D-69120
    • Glycotope Investigational Site
• Italy
  • Milan, Italy, 20132
    • Glycotope Investigational Site
  • Milan, Italy, 20133
    • Glycotope Investigational Site
• Switzerland
  • Bellinzona, Switzerland, CH-6500
    • Glycotope Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CetuGEX™, weekly; application weekly	Drug: CetuGEX™; Other Names: tomuzotuximab
Experimental: CetuGEX™ 2-weekly; application biweekly	Drug: CetuGEX™; Other Names: tomuzotuximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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)	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™	from first infusion until 28±2 days following the last infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	From date of randomization until the date of first documented progression, assessed up to 60 months
Anti-Tumor Activity: Clinical Benefit 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)	From date of randomization until the date of first documented progression, assessed up to 60 months
Eastern Cooperative Oncology Group (ECOG) Performance Status	The ECOG Scale of Performance Status describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). The scale comprises six grades: 0 Fully active, able to carry on all pre-disease performance without restriction; Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours; Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours; Completely disabled; cannot carry on any selfcare; totally confined to bed or chair; Dead	From date of randomization until 28 days ± 2 days after the end of treatment
Pharmacokinetics (PK): Area under the serum concentration-time curve (AUC)	PK of CetuGEX™ after single and multiple administration	Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks
Pharmacokinetics (PK): Maximum serum concentration (Cmax)	PK of CetuGEX™ after single and multiple administration	Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks
Pharmacokinetics (PK): Time to maximum serum concentration (tmax)	PK of CetuGEX™ after single and multiple administration	Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks
Pharmacokinetics (PK): Minimal serum concentration (Cmin)	PK of CetuGEX™ after single and multiple administration	Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks
Pharmacokinetics (PK): Terminal elimination half-life (t1/2)	PK of CetuGEX™ after single and multiple administration	Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks
Pharmacokinetics (PK): Clearance rate (CL)	PK of CetuGEX™ after single and multiple administration	Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks
Pharmacokinetics (PK): Volume of distribution (Vz)	PK of CetuGEX™ after single and multiple administration	Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks

Collaborators and Investigators

• Sponsor: Glycotope GmbH

Publications and helpful links

General Publications

• Fiedler W, Cresta S, Schulze-Bergkamen H, De Dosso S, Weidmann J, Tessari A, Baumeister H, Danielczyk A, Dietrich B, Goletz S, Zurlo A, Salzberg M, Sessa C, Gianni L. Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epidermal growth factor receptor, in patients with advanced carcinomas. ESMO Open. 2018 Feb 1;3(2):e000303. doi: 10.1136/esmoopen-2017-000303. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: October 15, 2010
• First Submitted That Met QC Criteria: October 15, 2010
• First Posted (Estimate): October 18, 2010

Study Record Updates

• Last Update Posted (Actual): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 20, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: advanced solid cancers; metastatic solid cancers
• Other Study ID Numbers: GEXMab52101