EA3202 – A Phase II/III Trial of Chemotherapy + Cetuximab vs. Chemotherapy + Bevacizumab vs. Atezolizumab + Bevacizumab Following Progression on Immune Checkpoint Inhibition in Recurrent/Metastatic Head and Neck Cancers

The study chair for this trial is Aarti Bhatia, MD, MPH (Yale University/Smilow Cancer Center). The study co-chairs are Jennifer Johnson, MD, PhD (Thomas Jefferson University/Sidney Kimmel Cancer Center), Jeffrey Ishizuka, MD (Yale University/Smilow Cancer Center), Rathan Subramaniam, MD, PhD, MPH, MBA (University of Otago), and Mei Tang, MD (Greater Baltimore Medical Center).

The NCTN group study champions are TBD for Alliance, Vidhya Karivedu, MBBS (The Ohio State University Comprehensive Cancer Center) for NRG Oncology, and Aarti Bhatia, MD, MPH (Yale University/Smilow Cancer Center) for SWOG.

The usual treatment for patients with recurrent and metastatic head and neck squamous cell carcinoma is therapy with immune checkpoint inhibitors. However, if the cancer begins to progress, the optimal second-line treatment is not yet known. The most common approach is chemotherapy plus EGFR inhibition—but pre-clinical and clinical evidence from recent studies suggest promising activity of other options, including vascular endothelial growth factor (VEGF) and programmed death-1 (PD-1) inhibitor combination therapy. The EA3202 study is a phase II/III trial of these alternatives.

In the phase II portion of EA3202, patients will be randomized equally to three arms. Arm A is the control arm of chemotherapy with the EGFR inhibitor cetuximab. There are two experimental arms. In Arm B, patients will receive chemotherapy with the VEGF inhibitor bevacizumab. In Arm C, patients will receive the PD-L1 inhibitor atezolizumab with bevacizumab. Investigators will select the experimental arm that performs significantly better than the control arm—as indicated by progression-free survival (PFS)—for evaluation against the control arm in the phase III portion.

During phase III, the primary objective will be to compare the overall survival (OS) of patients treated with chemotherapy plus cetuximab to the superior arm from phase II. Secondary objectives include evaluating the OS for the subset of patients with high PD-L1 expression on all arms of treatment, and assessing the toxicity of each arm of treatment.

In addition to the objectives above, EA3202 also has imaging objectives: to establish the correlation between 18F-FDG PET and CT neck imaging biomarkers and PD-L1 expression, and to determine if 18FDG-PET/CT and CT neck imaging biomarkers at baseline will predict treatment response at 9 to 12 weeks post-treatment, PFS, and OS.

Patients are eligible to participate in EA3202 if they have squamous cell carcinoma (SCC) of the head and neck, excluding SCC of the salivary glands and skin. They must have received prior therapy with an immune checkpoint inhibitor in the first-line setting for recurrent/metastatic disease, with stable disease for at least 12 weeks. Prior combination immunotherapies are permitted, but patients must not have had any prior chemotherapy, cetuximab, or any prior antiangiogenic treatment.

Learn more about EA3202 at ecog-acrin.org.