Cemiplimab Plus Fianlimab for the Treatment of Locally Advanced Head and Neck Basal Cell Carcinoma Before Surgery

The proposed study is a phase II trial of neoadjuvant Cemiplimab (cohort 1) or Cemiplimab plus Fianlimab (cohort 2) that will target patients with advanced BCCHN who have not been previously treated with anti-PD1 checkpoint therapy for this primary lesion. Patients will be assessed by the enrolling surgeon for response to therapy every 3 weeks (before initiating the next cycle) by clinical assessment, and by imaging assessment (every 6 weeks). Patients will undergo a minimum of 2 cycles of therapy over a 6-week window prior to surgery. Patients who demonstrate clinical or RECISTv1.1 response or stable disease with regression or up to 5% growth, will go on to the next cycle of treatment. Patients who demonstrate clinical or RECISTv1.1 radiographic progression or stable disease with \>5%-20% growth will proceed directly to surgery or to other SOC therapy (after biopsies) (Fig 1). Patients who demonstrate a complete clinical response prior to at any assessment prior to completion of 6 cycles will proceed to appropriate surgery or biopsy of tumor site to ensure complete pathologic response at the time of CR.

PRIMARY OBJECTIVE:

I. Our primary objective is to assess treatment response of locally advanced BCC of the head and neck (BCCHN) in the neoadjuvant, presurgical setting.

SECONDARY OBJECTIVES:

I. To assess functional organ preservation with neoadjuvant Cemiplimab or Cemiplimab plus Fianlimab therapy.

II. To assess pathologic response. III. To assess safety of neoadjuvant therapy. IV. To assess changes in quality of life.

EXPLORATORY OBJECTIVE:

I. To assess treatment-related changes in the immune microenvironment related to functional changes in immune cell composition.