Lovastatin and Pembrolizumab for the Treatment of Patients with Recurrent or Metastatic Head and Neck Cancer, LAPP Trial

Inclusion Criteria

• Adult patients, male or female, aged ≥ 18, able to provide informed consent
• Subjects with pathologically proven, recurrent or metastatic HNSCC involving the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, or paranasal sinuses; patients with unknown primary HNSCC involving the cervical lymph nodes can be included if human papillomavirus (HPV)-positive
• PD-L1 combined positive score (CPS) ≥ 1 (i.e., must be a candidate for treatment with pembrolizumab alone)
• Patients must not be under consideration for salvage surgery
• Measurable disease by RECIST 1.1 criteria
• Life expectancy of more than 3 months, as determined by the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Recovery to baseline or ≤ grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4.0 from toxicities related to any prior treatments, unless adverse events are clinically non-significant and/or stable on supportive therapy
• For men or women of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 8 weeks after the end of lovastatin/pembrolizumab administration
• Absolute neutrophil count (ANC) ≥ 1000/mm^3 without colony stimulating factor support
• Platelets ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• Bilirubin ≤ 1.5 x the upper limit of normal (ULN). For subjects with known Gilbert’s disease, bilirubin ≤ 3.0 mg/dL
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 x ULN

Exclusion Criteria

• Patients already taking a statin drug within the past 4 weeks
• Liver dysfunction precluding the use of statins
• Radiation to the head and neck or other sites within 4 weeks prior to enrollment
• Cytotoxic chemotherapy or any form of investigational therapy within 4 weeks prior to study treatment
• Prior treatment with immune checkpoint blocking therapy
• Current use of drugs that interact with lovastatin (cimetidine, spironolactone, ketoconazole, and others)
• Pregnancy, lactation, or plan to become pregnant
• Inability to swallow lovastatin tablets
• Known allergy or prior adverse reaction to lovastatin, other statin drugs, or pembrolizumab