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

PRIMARY OBJECTIVE:

I. To evaluate anti-tumor activity of the combination of pembrolizumab and lovastatin by assessing the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

SECONDARY OBJECTIVE:

I. To evaluate the anti-tumor activity of the combination of by assessing progression-free survival (PFS) and overall survival (OS).

TERTIARY/EXPLORATORY OBJECTIVES:

I. To assess the effects of the combination of lovastatin + pembrolizumab on immune cells in blood.

II. To assess the association between efficacy measures and expression in tumors.

III. To assess the association between anti-tumor activity and immune cells in the blood.

OUTLINE:

Patients receive lovastatin orally (PO) once daily (QD) and pembrolizumab intravenously (IV) over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT throughout the study.

After completion of study treatment, patients are followed for up to 2 years.

Inclusion criteria

• Adult patients, male or female, aged ≥ 18, able to provide informed consent
• Subjects with pathologically proven, recurrent or metastatic head and neck squamous cell carcinoma (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.)5.0 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 albumin ≥ 2.8 g/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
• Serum phosphorus, calcium, magnesium and potassium ≥ lower limit of normal (LLN)

Exclusion criteria

• Patients already taking a statin drug
• 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