Lenvatinib and Pembrolizumab for Recurrent Respiratory Papillomatosis with Lung Involvement
This study is testing Lenvatinib (a pill taken by mouth daily) and Pembrolizumab (given through an IV every three weeks) in adults with recurrent respiratory papillomatosis (RRP) that affects the lungs. RRP is a condition caused by the human papillomavirus (HPV) that causes growths in the airways. Researchers want to see how many people respond to this treatment and if it is safe. You can join if you are 18 or older and have RRP with lung involvement confirmed by a biopsy. The study plans to enroll 20 participants and is currently unclear about its recruitment status.
- Study design
- This is a pilot study that is not randomized, meaning participants are not assigned to different treatment groups by chance. It will enroll 20 adult participants.
- What's involved
- You would take Lenvatinib daily and receive Pembrolizumab every three weeks. You will have clinic visits every three weeks, operating room evaluations every 12 weeks, and chest CT scans every 12 weeks for up to two years or until treatment ends. You will also complete quality of life questionnaires.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your response to treatment will be measured for up to two years and/or until the end of treatment. Adverse events will be monitored every three weeks for up to two years and/or until the end of treatment.
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NCT04645602
Merck IIT: RRP Pembro and Lenvatinib
Recruiting
PHASE2Ages 18+InterventionalTreatmentYale UniversityInvestigator-initiated
~20 participants
Updated 2026-07-02 on ClinicalTrials.gov
What's tested:LenvatinibPembrolizumab
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Objective Response Rate (ORR)
Measured over At 12 weeks for up to 2 years and/or end of treatment
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesConnecticut1
Study leadership
- Sara I Pai, MD, PHD · PRINCIPAL_INVESTIGATOR · Yale University
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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:
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 \>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.
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.
Female subject of childbearing potential must have a negative serum pregnancy test within 28 days of the first dose of study drug\*. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
Is not a WOCBP as defined below. OR
Is a WOCBP and must be willing to use 2 methods of birth control, or abstain from heterosexual activity during the intervention period and for at least 120 days after the last dose of pembrolizumab or 30 days post lenvatinib, whichever occurs last.
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months (or 120 days) after completion of pembrolizumab
Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of Lenvatinib:
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed
Ability to complete Patient Medication and Blood Pressure diaries by themselves or with assistance.
Ability to understand and the willingness to sign a written informed consent document.
Exclusion
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study enrollment.
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.
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 \> 2+ (greater than or equal to100 mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
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 \>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.
Has clinically significant gastrointestinal malabsorption syndrome or any other condition that might affect the absorption of lenvatinib.
Has preexisting greater than or equal to Grade 3 gastrointestinal or non-gastrointestinal fistula
Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
Has a known history of posterior reversible encephalopathy syndrome (PRES).
Participants with history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Participants with psychiatric illness/social situations that would limit compliance with study requirements.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab and/or lenvatinib, and breastfeeding should be discontinued.
What this trial measures
- Objective Response Rate (ORR)At 12 weeks for up to 2 years and/or end of treatment
To evaluate the best objective response rate (ORR: CR/PR) in subjects with RRP with measurable or evaluable pulmonary involvement based on RECIST 1.1 and the endoscopic lesional burden score
- Adverse EventsEvery 3 weeks for up to 2 years and/or end of treatment
To evaluate the safety and tolerability of the combination of pembrolizumab and lenvatinib in subjects with RRP as measured by the number of participants experiencing adverse events