Summary

This phase II trial studies how well avelumab with or without cetuximab work in treating patients with skin squamous cell cancer that has spread to other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as avelumab and cetuximab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Objectives

PRIMARY OBJECTIVE:
I. To evaluate whether treatment with avelumab plus cetuximab prolongs progression free survival (PFS) compared to avelumab alone.

SECONDARY OBJECTIVES:
I. To evaluate the confirmed objective response rate of each treatment arm.
II. To evaluate the clinical benefit rate of each treatment arm.
III. To evaluate the PFS of cetuximab plus avelumab in patients that have progressed on single agent avelumab.
IV. To evaluate the overall survival (OS) for each treatment arm.
V. To evaluate toxicity across treatment arms of avelumab plus cetuximab and avelumab alone.

CORRELATIVE OBJECTIVE:
I. To examine the association between PD-L1 expression and response rate (RR), clinical benefit rate (CBR), PFS and OS in both patients receiving cetuximab and avelumab as well as avelumab alone.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive avelumab intravenously (IV) over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with avelumab failure will crossover to arm II. Patients also undergo collection of blood and computed tomography (CT) or magnetic resonance imaging (MRI) throughout study.

ARM II: Patients receive cetuximab IV over 2 hours on days 1 and 15 and avelumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles for cetuximab and 24 cycles for avelumab in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and CT or MRI throughout study.

After completion of study treatment, patients are followed up every 3 months until disease progression, then every 6 months for up to 2 years.