Afatinib for the Treatment of Advanced Cutaneous Squamous Cell Carcinoma

Inclusion Criteria

• Age >= 18 years at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
• Absolute neutrophil count (ANC) >= 1.0 x 109/L
• Hemoglobin >= 8 g/dL
• Platelets >= 75 x 109/L.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x ULN.
• Calculated creatinine clearance > 15 mL/min by Cockroft-Gault formula.
• Histologic diagnosis of invasive cutaneous squamous cell carcinoma, that is deemed not appropriate for further surgical intervention and/or radiation therapy. Patients may have either locally advanced or metastatic disease.
• At least 1 measurable lesion - either per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or for patients with externally visible cuSCC lesion(s) not measurable on imaging, at least one lesion >= 1 cm in longer diameter, amenable to digital photography with bi-dimensional measurements.
• Patients must have received prior immunotherapy with an anti-PD-1/PD-L1 antibody, if patient was deemed eligible (i.e., was not immunosuppressed or a transplant receipt, etc).
• Immunosuppressed patients including those with concurrent autoimmune diseases and solid organ transplant recipients are eligible.
• Prior to first dose of study treatment, patients must be at least 2 weeks from any prior systemic therapy, major surgery or radiation.
• Able to undergo a pre-treatment and on-treatment tumor biopsy.
• Female participants of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (beta‑HCG) test result. Female participants of childbearing potential and male participants must agree to use methods of contraception that are highly effective.
• Patients with brain metastases are permitted assuming that the brain metastases have been adequately treated with prior surgery or radiation.

Exclusion Criteria

• In patients with known liver cirrhosis, those with severe (Child Pugh C) hepatic impairment will be excluded.
• Untreated, uncontrolled or symptomatic brain metastases or leptomeningeal carcinomatosis that are not stable or require corticosteroids.
• Patients with mixed histologies (eg, sarcomatoid, adenosquamous) will generally not be eligible, unless the predominant histology is invasive cuSCC.
• Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to randomization. Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load prior to randomization.
• Pregnancy or breast feeding.