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

NCT06636734 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00007740NCI-2024-06118WINSHIP6229-24P30CA138292
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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; Metastatic Nasopharyngeal Squamous Cell Carcinoma; Metastatic Oral Cavity Squamous Cell Carcinoma; Metastatic Oropharyngeal Squamous Cell Carcinoma; Metastatic Paranasal Sinus Squamous Cell Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Nasopharyngeal Squamous Cell Carcinoma; Recurrent Oral Cavity Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Paranasal Sinus Squamous Cell Carcinoma; Stage IV Hypopharyngeal Carcinoma AJCC v8; Stage IV Laryngeal Cancer AJCC v8; Stage IV Lip and Oral Cavity Cancer AJCC v8; Stage IV Nasopharyngeal Carcinoma AJCC v8; Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8; Stage IV Sinonasal Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR will be defined as the proportion of subjects with partial response or complete response. ORR will be evaluated using Response Evaluation Criteria in Solid Tumors version (RECIST) (v)1.1 response criteria. ORR will be calculated with 95% confidence interval by binomial distribution.

  Up to 1 year

Secondary Outcomes (3)

• Progression free survival (PFS)

  From date of treatment start to the date of objectively documented progression or death due to any cause, whichever status is recorded first, assessed up to 1 year

• Overall survival (OS)

  Up to 1 year

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  Up to 30 days after last dose of study treatment

Study Arms (1)

Treatment (lovastatin, pembrolizumab)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Lovastatin; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Procedure: Positron Emission Tomography

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (lovastatin, pembrolizumab)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (lovastatin, pembrolizumab)

Lovastatin DRUG

Given PO

Also known as: Lovastatin Sodium, Mevacor, Mevinolin, Monacolin K

Treatment (lovastatin, pembrolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (lovastatin, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, QL2107, SCH 900475, SCH-900475, SCH900475

Treatment (lovastatin, pembrolizumab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (lovastatin, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Mouth Neoplasms; Nasopharyngeal Carcinoma; Carcinoma

Interventions

Specimen Handling; Lovastatin; Magnetic Resonance Spectroscopy; pembrolizumab

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Mouth Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Nicole C Schmitt, D, FACS

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicole C. Schmitt, MD, FACS

CONTACT

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

Nabil F Saba, MD, FACP

CONTACT

404-778-1900; nfsaba@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 8, 2024
• First Posted: October 15, 2024
• Study Start: December 9, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

US (2)