This study is for subjects who have been diagnosed with recurrent or metastatic nasopharyngeal cancer. Subjects are expected to remain in the study for a minimum of 70 months. Drugs are FDA approved and is given through a vein (also called IV or intravenous). The procedures include blood and urine tests, troponin test. Risks include infection, bruising, bleeding, anemia, kidney damage, hearing loss, nausea, vomiting, numbness, pain, rash, blood in urine. You may not receive a benefit from participating in this trial, however, information learned from the trial may help other people in the future.

The purpose of this study is to test whether adding cetuximab to standard of care (pembrolizumab) is more effective in shrinking tumor size and increasing survival when compared to being treated with pembrolizumab alone. This study seeks to find if this approach is the same, better, or worse than standard of care for returning or spreading head and neck cancer after previous treatment.

Treatment and follow up for this study may be up to 5 years. The procedures include blood tests, CT or MRI scans, and chemotherapy. Risks include tiredness, anemia, constipation, loss of appetite, joint stiffness, cough, swelling and redness of the skin.

You may or may not receive a direct benefit from participating in this trial, however, information learned from the trial may help other people in the future. Both drugs, pembrolizumab and cetuximab, are already individually approved by the FDA for use in head and neck cancers. However, the benefit of combining the two drugs is being investigated in this study and this study approach is not FDA approved.

There will be about 158 people taking part in this study, approximately 4 subjects will be enrolled at MUSC.