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

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