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Squamous Cell Carcinoma of Head and Neck

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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.

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.

EMD 1201081

Philip Breitfeld, MD

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.

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

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)

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.

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.

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.

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.

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.

EMD Serono

An AE is 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 IMP, regardless of causal relationship and even if no IMP has been administered.

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) and EMD 1201081 weekly (0.32 milligram per kilogram \[mg/kg\] by subcutaneous injection) was administered in 3-week treatment cycle until disease progression. Participants who had discontinued cetuximab due to toxicity in cetuximab monotherapy arm, continued to receive EMD 1201081 monotherapy until disease progression or participant elected to withdraw from the trial. The total treatment period was approximately 18 months.

Cetuximab Plus EMD 1201081

Cetuximab weekly (initial dose 400 mg/m\^2 over 120 minutes followed by 250 mg/m\^2 intravenous infusion over 60 minutes) was administered in 3-week treatment cycle until disease progression. Participants who had discontinued cetuximab due to toxicity of cetuximab monotherapy, continued to receive EMD 1201081 monotherapy until disease progression or participant elected to withdraw from the trial. The total treatment period was approximately 18 months.

Cetuximab Monotherapy

Total

Age, Continuous

Gender

Intent-to-treat (ITT) population included all the randomized participants who had received study treatment.

Few of the secondary outcome measures were planned and later removed due to Sponsor's decision to discontinue development of EMD 1201081. Overall survival data was analyzed only for participants who received EMD 1201081 plus cetuximab.

Merck KGaA Communication Center

ITT population included all the randomized participants who had received study treatment.

Progression-free Survival (PFS) Time: Independent Read Assessments

Percentage of Participants With Objective Response: Independent Read Assessments

Percentage of Participants With Disease Control: Independent Read Assessments

ITT population included all the randomized participants who had received study treatment. Overall survival data was analyzed only for participants who received cetuximab plus EMD 1201081.

Overall Survival (OS) Time

TEAEs

Serious TEAEs

Safety population included all the participants who received at least 1 dose study drug.

Spots Global Cancer Trial Database for recurrent or metastatic squamous cell carcinoma of the head and neck cancer