Merck IIT: RRP Pembro and Lenvatinib

Recruiting now · Phase 2

Conditions studied: Human Papilloma Virus, Recurrent Respiratory Papillomatosis, Pulmonary Disease

In brief

This research study is studying Lenvatinib in combination with Pembrolizumab in people with human papillomavirus (HPV)-associated recurrent respiratory papillomatosis (RRP). The names of the study drugs involved in this study are: * Pembrolizumab * Lenvatinib

Key facts

Study ID: NCT04645602
Run by: Yale University
People needed: 20
Starts: 2025-07-18
Expected to finish: 2027-12-01
Last updated by the study team: 2026-07-02

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Participants must have histologically or cytologically confirmed respiratory papillomas with radiologic evidence of lung involvement. Subjects can have measurable or non-measurable* pulmonary disease based on RECIST 1.1. Non-measurable disease based on RECIST 1.1 is defined as lesions with a short axis less than 10 mm
For those patients with non-measurable pulmonary disease, participants must have disease at other sites such as the larynx and trachea and must have undergone > 3 surgical procedures over a 12-month period.
Be required to provide tissue from a newly obtained biopsy of a lesion or an archived specimen. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to the first dose of study drug. Subjects for whom newly obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the PI.
Have confirmed human papillomavirus-associated lesions based on in-situ hybridization testing and/or polymerase chain reaction which may be performed on a newly obtained biopsy or archived sample.
Age ≥18 years.
ECOG performance status of 0 to 1.
Participants must have adequate organ and marrow function as defined below:
--- Absolute neutrophil count (ANC) ≥1500/μL
--- Platelets ≥100 000/μL
--- Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (a)
Creatinine OR Measured or calculated (b) creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × institutional ULN OR ≥30 mL/min for participant with creatinine levels \&amp;gt;1.5 × institutional ULN
Total bilirubin ≤1.5 × institutional ULN OR direct bilirubin ≤ institutional ULN for participants with total bilirubin levels greater than or equal to 1.5× institutional ULN
AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × institutional ULN for participants with liver metastases)
TSH Institutional normal limit
Free T4 Institutional normal limit
Amylase less than or equal to 1.5 x institutional ULN
Lipase less than or equal to 1.5 x institutional ULN
International normalized ratio (INR) OR prothrombin time (PT)
Activated partial thromboplastin time (aPTT)
1.5 × institutional ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC)transfusion within last 2 weeks.
Creatinine clearance (CrCl) should be calculated per institutional standard. -- Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
Adequately controlled blood pressure with or without antihypertensive medications defined as systolic BP ≤ 140 mmHg and diastolic BP ≤ 90 mmHg at screening with no change in antihypertensive medications within 1 week prior to screening.

You may not qualify if…

Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study enrollment.
Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. Withhold lenvatinib for at least 7 days prior to elective major surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. Endoscopic debridement of RRP lesions is NOT considered a major surgery.
Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
Has had major surgery within 3 weeks prior to first dose of study interventions. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
Is currently participating in or has participated in a study of an investigational agent within 4 weeks prior to the first dose of study treatment. NOTE: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. NOTE: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, well-differentiated thyroid cancer, follicular lymphoma, carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) invasive cancer derived from RRP, or other indolent malignancy not requiring active treatment are not excluded.
History of allergic reactions (greater than or equal to Grade 3) attributed to compounds of similar chemical or biologic composition to pembrolizumab or lenvatinib and/or any of its excipients.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
Has an active infection requiring systemic therapy.
Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. NOTE: No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
Has a known history of active TB (Bacillus Tuberculosis).
Has urine protein greater than or equal to 1 g/24 hours. Note: Participants with proteinuria \&gt; 2+ (greater than or equal to100 mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
Note: Urine dipstick is the preferred method for testing urinary protein, however, urinalysis may be used if the use of urine dipsticks is not feasible.
Electrolyte abnormalities that have not been corrected.
Has clinically significant cardiovascular disease within 12 months from first dose of study intervention: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia associated with hemodynamic instability and requiring medical treatment at screening. Note: Medically controlled arrhythmia would be permitted.
Has a LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
Prolongation of QTcF interval to \&gt;480 msec, as calculated by either the Bazett or Fridericia formula, as per institutional standard.
Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
Has a known history of colitis.

Where it is running

Yale University — New Haven, Connecticut, United States (enrolling)

Full record on ClinicalTrials.gov

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