Recruiting
Phase 2

Lovastatin & Pembrolizumab

Sponsor:

Emory University

Code:

NCT06636734

Conditions

Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Human Papillomavirus-Related Neck Squamous Cell Carcinoma of Unknown Primary

Metastatic Head and Neck Squamous Cell Carcinoma

Metastatic Hypopharyngeal Squamous Cell Carcinoma

Metastatic Laryngeal Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Computed Tomography

Lovastatin

Magnetic Resonance Imaging

Pembrolizumab

Study Details

Brief summary:

This phase II trial tests how well lovastatin and pembrolizumab work in treating patients with head and neck cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Lovastatin is a drug used to lower the amount of cholesterol in the blood and may also cause tumor cell death. In addition, studies have shown that lovastatin may make the tumor cells more sensitive to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lovastatin and pembrolizumab may kill more tumor cells in patients with recurrent or metastatic head and neck cancer.

Conditions

Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Human Papillomavirus-Related Neck Squamous Cell Carcinoma of Unknown Primary

Metastatic Head and Neck Squamous Cell Carcinoma

Metastatic Hypopharyngeal Squamous Cell Carcinoma

Metastatic Laryngeal Squamous Cell Carcinoma

Study ID

NCT06636734

Start date

Dec 9, 2024

Status verified date

Feb, 2026

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

28 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (lovastatin, pembrolizumab)

Patients receive lovastatin PO QD and pembrolizumab 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 CT, MRI or PET/CT throughout the study.

Interventions

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo CT or PET/CT

Lovastatin

Given PO

Magnetic Resonance Imaging

Undergo MRI

Pembrolizumab

Given IV

Positron Emission Tomography

Undergo PET/CT

Primary outcome measure

  • Objective response rate (ORR) [ Time Frame: Up to 1 year ]

Central Contacts and Locations

Central contacts

Nicole C. Schmitt, MD, FACS

404-778-0278nicole.cherie.schmitt@emory.edu

Nabil F Saba, MD, FACP

404-778-1900nfsaba@emory.edu

Locations

Emory University Hospital Midtown

Recruiting

Atlanta, Georgia, United States, 30308

Contacts

Ardith Deshay

404-686-1858ardith.deshay.deshay@emory.edu

Principal Investigator:

Nicole C. Schmitt, MD, FACS

Emory University Hospital/Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Ardith C. Deshay

404-686-1858ardith.deshay.deshay@emory.edu

Principal Investigator:

Nicole C. Schmitt, MD, FACS

More Information

Sponsor

Emory University

Last update posted

Feb 11, 2026

Last verified

Feb, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Emory University on 2026-02-11.