EMD 1201081 in Combination With Cetuximab in Second-Line Cetuximab-Naïve Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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The purpose of this study is to determine if EMD 1201081 in combination with cetuximab is more efficient than cetuximab alone to control the cancer. EMD 1201081 is an immune modulatory oligonucleotide (IMO) containing phosphorothioate oligodeoxynucleotide and acts as an agonist of Toll-like receptor 9 (TLR9). EMD 1201081 has been studied in six clinical trials in over 170 subjects either as a monotherapy or in combination with chemotherapeutic agents or targeted therapies. Two studies have been conducted in healthy volunteers. In the other five studies, subjects with advanced solid tumors, renal cell carcinoma, non-small cell lung cancer and colorectal cancer have been treated with EMD 1201081. Two studies are still ongoing. Future clinical development of EMD 1201081 will focus on colorectal cancer (CRC) and squamous cell cancer of the head and neck (SCCHN). In this Phase 2 study, subjects with recurrent or metastatic squamous cell cancer of the head and neck (R/M SCCHN), will be treated with cetuximab plus EMD 1201081 or cetuximab alone. The study will be conducted as a multicenter study in several European Union (EU) member states and the Unites States. EMD 1201081 in combination with cetuximab will be evaluated for antitumor activity in subjects by examining its effects on accepted clinical endpoints. Progression-free survival (PFS) will be evaluated in subjects treated with EMD 1201081 plus cetuximab compared to cetuximab alone in cetuximab-naïve subjects with R/M SCCHN who have progressed on a cytotoxic therapy. Cetuximab, approved in colorectal cancer and SCCHN in combination with platinum-based chemotherapy and SCCHN in combination with radiotherapy in the EU, will be provided as investigational medicinal product (IMP) in this study. Commercially available Cetuximab will be provided in the United States.

Official Title
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A Phase II, Open-label, 1:1 Randomized, Controlled Trial Exploring the Efficacy of EMD 1201081 in Combination With Cetuximab in Second-Line Cetuximab-Naïve Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN)

Conditions
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Squamous Cell Carcinoma of the Head and Neck Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: EMD 1201081


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written informed consent prior to any trial-specific procedure Male or female subjects age greater than or equal to (>=) 18 years with R/M SCCHN Histologically confirmed R/M SCCHN, documented in the medical record History of progressing disease on a first-line cytotoxic chemotherapy regimen for R/M SCCHN, such as 5-fluorouracil (FU) plus cisplatin, or taxanes. (A history of chemotherapy or radiotherapy for localized disease was not considered a first-line regimen) The subject is suited for systemic therapy in the opinion of the Investigator At least one radiographically documented lesion measurable according to response evaluation criteria in solid tumors (RECIST) 1.0. All target lesions are to be measurable (that is, the lesion must be adequately measurable in at least one dimension; longest diameter to be recorded as >= 2 centimeter (cm) by conventional techniques or >= 1 centimeter (cm) by spiral computed tomography [CT] scan). Target lesions are to be selected from the required protocol imaging. If the sole site of measurable disease is in a prior radiation field, there has to be unequivocal evidence of progression at >= 8 weeks since the completion of radiation or a positive biopsy Eastern cooperative oncology group performance status (ECOG PS) of 0 or 1 If female, either post-menopausal, surgically sterile, or having a negative urine or serum pregnancy test (beta-human chorionic gonadotropin [beta-HCG]) at screening and practicing medically accepted contraception. If male, practicing contraception if the risk of conception exists. For relevant subjects, the duration of contraception should be 1 week prior to the start of therapy through 4 weeks after receipt of trial therapy Recovered from previous toxicities of prior cytotoxic regimen to common terminology criteria of adverse events (CTCAE) Grade 1 (with the exception of alopecia) Hemoglobin >= 9 gram per deciliter (g/dL) without transfusion support; no transfusion within 7 days prior to screening) Neutrophils >= 1.5 * 10^9 per liter Platelets >= 100 * 10^9 per liter Prothrombin time/partial thromboplastin time (PT/PTT) less than or equal to (=<) 1.5 times the upper limit of normal (ULN) for the site, unless there is therapeutic anti-coagulation Serum creatinine =< 1.5 times the ULN for the site Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 times the ULN for the site Be willing and able to comply with the protocol procedures for the duration of the trial Exclusion Criteria: History of prior exposure to cetuximab or panitumumab or any other approved or investigational anti-epidermal growth factor receptor (EGFR) agents Undifferentiated nasopharyngeal carcinoma Chemotherapy, radiotherapy or any investigational agents within 4 weeks prior to first dose of study drug Major surgical or planned procedure within 30 days prior to first dose of trial medication (isolated biopsies are not considered major surgical procedures) Active malignancy other than SCCHN, non-metastatic basal cell or squamous cell carcinoma of the skin, or second primary SCCHN Impaired cardiac function (for example, left ventricular ejection fraction less than [<] 45 percent defined by echocardiograph or other study), history of uncontrolled serious arrhythmia, unstable angina pectoris, congestive heart failure (new york heart association [NYHA] Grade III and IV), myocardial infarction within the last 12 months prior to trial entry, or signs of pericardial effusion Hypertension uncontrolled by standard pharmacologic therapies History of diagnosed interstitial lung disease Subject requires systemic anti-coagulation (example, warfarin greater than [>] 10 milligram per day [mg/day]) Pregnancy or breastfeeding Legal incapacity or limited legal capacity Significant medical or psychiatric disease which makes the trial inappropriate in the Investigator's opinion Any brain metastasis and/or leptomeningeal disease (known or suspected) Significant pre-existing immune deficiency, such as infection of human immuno-deficiency virus (HIV) (documented or known) Clinically significant ongoing infection Known hypersensitivity to the trial treatments Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer from such disease Other significant disease that in the Investigator's opinion would exclude the subject from the trial

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab plus EMD 1201081<br> | Drug: Cetuximab<br>* Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] over 120 minutes followed by 250 mg/m^2 intravenous infusion over 60 minutes) will be administered in 3-week treatment cycle until disease progression. The total treatment period will be approximately 18 months.<br>* Other names: Erbitux®;Drug: EMD 1201081<br>* EMD 1201081 weekly (0.32 milligram per kilogram [mg/kg] by subcutaneous injection) will be administered in 3-week treatment cycle until disease progression. Subjects who will discontinue cetuximab due to toxicity in cetuximab monotherapy, could continue to receive EMD 1201081 monotherapy until disease progression. The total treatment period will be approximately 18 months.<br>* Other names: IMO-2055;|
| Active Comparator: Cetuximab monotherapy<br> | Drug: Cetuximab<br>* Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] over 120 minutes followed by 250 mg/m^2 intravenous infusion over 60 minutes) will be administered in 3-week treatment cycle until disease progression. The total treatment period will be approximately 18 months.<br>* Other names: Erbitux®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Time: Independent Read Assessments | The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause within 60 days of the last tumor assessment or randomization. Participants without event were censored on the date of last tumor assessment. | Every 6 weeks until disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, 17 Dec 2009 until cut-off date (11 Jan 2012) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response: Independent Read Assessments | Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) as assessed by Independent Read. As per RECIST v1.0 for target lesions and assessed by MRI: CR = Disappearance of all target lesions; PR = at least 30% decrease in the sum of the longest diameter of target lesions. | Every 6 weeks until disease progression, reported between day of first participant randomized, that is, 17 Dec 2009 until cut-off date (11 Jan 2012) | 
| Percentage of Participants With Disease Control: Independent Read Assessments | Percentage of participants with disease control, defined as having achieved CR or PR or stable disease (SD) as the tumor response according to radiological assessments (based on RECIST Version 1.0 criteria), was reported. As per RECIST v1.0 for target lesions and assessed by MRI: CR = disappearance of all target lesions; PR = at least 30% decrease in the sum of the longest diameter of target lesions; SD = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. | Every 6 weeks until disease progression, reported between day of first participant randomized, that is, 17 Dec 2009 until cut-off date (11 Jan 2012) | 
| Overall Survival (OS) Time | The overall survival (OS) time was defined as the time from randomization to death. Participants without event were censored at the last date known to be alive or at the clinical cut-off date, whatever was earlier. | Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, 17 Dec 2009 until cut-off date, (11 Jan 2012) | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. A Serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. | Time from first dose up to Day 42 to 49 after last dose of trial treatment, reported between day of first participant randomized, that is, 17 Dec 2009 until cut-off date, (11 Jan 2012) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Cancer, Cetuximab, EMD 1201081