CetuGEX™ in Comparison to Cetuximab for the Treatment of Patients With Head and Neck Cancer

Randomized, Controlled, Open Label, Multicenter, Phase II Study to Evaluate the Efficacy and Safety of CetuGEX™ Plus CT in Comparison to Cetuximab Plus CT in Patients With Stage III/IV Recurrent and/or Metastatic SCCHN

The aim of the study is to evaluate the efficacy of CetuGEX™ for the treatment of patients with stage III/IV recurrent and/or metastatic SCCHN as compared to cetuximab (both in combination with platinum-based chemotherapy) in terms of progression-free survival (PFS).

Indication: First line systemic treatment for stage III/IV recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN)

Primary Objective:

To evaluate the efficacy of CetuGEX™ for the treatment of patients with stage III/IV recurrent and/or metastatic SCCHN as compared to cetuximab (both in combination with platinum-based chemotherapy) in terms of progression-free survival (PFS).

Secondary Objectives:

To evaluate further efficacy criteria, safety and quality of life (QoL) of patients with stage III/IV recurrent and/or metastatic SCCHN treated with CetuGEX™ as compared to cetuximab (both in combination with platinum-based chemotherapy).

To assess pharmacokinetic (PK) parameters and profiles of CetuGEX™. To assess efficacy and safety based on genetic markers for immune response (Fc-gamma receptor [FcγR] allotypes) and biomarkers (exploratory only).

Inclusion Criteria:

1. Patients with histologically confirmed recurrent and/or metastatic SCCHN not eligible for local treatment.
2. Patients with measurable disease according to RECIST 1.1.
3. Patients aged at least 18 years at screening.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Minimum life expectancy of 3 months.
6. Tissue samples available for specific and therapy-related biological assessments.
7. If female and of childbearing potential, was non-lactating and had negative pregnancy test results at screening and prior to randomization.
8. If female, was either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or hysterectomy]) or willing to use highly effective contraceptives during study participation until 6 months after last administration of any study medication, particularly cisplatin or carboplatin, with a failure rate <1% according to the Note for Guidance on non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals (CPMP/ICH/286/95) of the European Medicines Agency. Male patients who had partners of childbearing potential had to confirm adequate use of highly effective contraceptives during study participation until 6 months after last administration of any study medication, particularly cisplatin or carboplatin, as well.
9. Willing and able to comply with the protocol.
10. Willing and able to provide written informed consent.

Exclusion Criteria:

1. Prior systemic chemotherapy, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to randomization.
2. Cetuximab or other epidermal growth factor receptor (EGFR)-targeting agent treatment, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to randomization.
3. Surgery (other than minor interventions like diagnostic biopsy or intravenous port implantation) or irradiation within 30 days before randomization.
4. Concomitant antitumor therapy or concomitant immunotherapy, live vaccines including yellow fever vaccination (as per cisplatinum Summary of Product Characteristics [SmPC]).
5. Concomitant corticosteroid treatment unless specified within the protocol.
6. Clinical evidence of brain metastasis or leptomeningeal involvement.
7. Patients with nasopharyngeal tumors.
8. Concomitant malignant disease, except for adequately treated tumors with high likelihood of being cured (e.g., basal cell cancer of the skin, cervical cancer or breast cancer in situ). Patients with previous malignancies but without evidence of disease for at least 5 years were allowed to enter the study.
9. Patients with renal or hepatic impairment (serum creatinine and bilirubin >1.5 fold above the upper limit of normal ranges, creatinine clearance <60 mL/min, and transaminase >5-fold above the upper limit of normal ranges) and patients with hematology parameters outside the normal ranges (hemoglobin <9 g/dL, absolute neutrophil count <1500/mm3 and platelet count <105/mm3) at screening as well as patients with impaired auditory function or platinum-related neuropathy.
10. Clinically active infections ≥Grade 2 using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 and/or requiring intravenous antibiotics.
11. Known active hepatitis B or C.
12. Known human immunodeficiency virus (HIV) infection.
13. Myocardial infarction within 6 months prior to screening.
14. Symptomatic congestive heart failure (New York Heart Association Grade 3 or 4), unstable angina pectoris within 6 months prior to screening, significant cardiac arrhythmia, history of stroke, or transient ischemic attack within 1 year prior to screening.
15. History of keratitis requiring medical interventions within the last 5 years or interstitial lung disease.
16. Patients with any other disorder that, in the opinion of the investigator, might have interfered with the conduct of the study.
17. Patients with an unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol abuse, interfering with study compliance, within 6 months prior to screening) or otherwise thought to be unreliable or incapable of complying with the requirements of the protocol.
18. Patients institutionalized by official means or court order.
19. Receipt of any other IMP within the last 30 days before randomization or any previous CetuGEX™ administration.
20. Prior allergic reaction to a monoclonal antibody, grade 3 infusion related reaction (IRR) or any grade 4 reaction to a monoclonal antibody.
21. Known sensitivity to any component of the IMP and medication used in this study.
22. Known dihydropyrimidine dehydrogenase deficiency (France only).