Avelumab, Cetuximab, and Palbociclib in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

This is an open-label phase I trial with a 3+3 dose escalation design. All patients will receive avelumab, cetuximab, and palbociclib. This study will enroll patients with head and neck squamous cell carcinoma not amenable to curative intent therapy.

Treatment will be administered in 28 day cycles with a pre-defined dose escalation schedule.

• Drug: Avelumab
  Avelumab (IV on days 1 and 15 of 28 day cycle)
  Other Name: Bavencio
• Drug: Palbociclib

  Palbociclib (PO daily, days 1-21 of 28 day cycle)

  Palbociclib will be administered in capsules of 125 mg, 100 mg, and 75 mg, depending on dosage. Patients will be instructed to take their assigned dose once daily with food for 21 days followed by 7 days off therapy. Patients will be encouraged to take their dose at approximately the same time each day.

  Other Name: IBRANCE
• Drug: Cetuximab

  Cetuximab (IV 400 mg/m2 x 1, then weekly)

  Cetuximab is administered intravenously once weekly via infusion pump or syringe pump with infusion rate not to exceed 10 mg/min.

  Other Name: ERBITUX

Inclusion Criteria:

• Histologically or cytologically proven squamous cell carcinoma of the head and neck not amenable to curative intent therapy.
• Presence of measurable tumor lesions per RECIST criteria v1.1
• Life expectancy greater than 12 weeks.
• Adequate hematologic, hepatic, and renal function
• Negative serum or urine pregnancy test for women of child bearing potential

Exclusion Criteria:

• Prior therapy with an EGFR inhibitor or PD-1 or PD-L1 inhibitor in the recurrent or metastatic setting
• Uncontrolled central nervous system metastases (stable metastases permitted)
• Chemotherapy 28 days prior to first administration of study treatment and/or monoclonal antibody ?8 weeks prior to first administration of study treatment.
• History of other malignancies,
• Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration of >10 mg/day of prednisone or equivalent)
• Prior organ transplantation
• Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).