Merck IIT: RRP Pembro and Lenvatinib

NCT04645602 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: HIC 2000035849
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Human Papilloma Virus; Recurrent Respiratory Papillomatosis; Pulmonary Disease

Keywords

Human Papilloma Virus; Recurrent Respiratory Papillomatosis; Pulmonary Involvement

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  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

  At 12 weeks for up to 2 years and/or end of treatment

• Adverse Events

  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

  Every 3 weeks for up to 2 years and/or end of treatment

Secondary Outcomes (3)

• Objective Response Rate

  Baseline to a post-baseline timepoint up to 2 years and/or end of treatment

• Change in Time Interval

  Baseline to a post-baseline timepoint up to 2 years and/or end of treatment

• Duration of Response

  Baseline to a post-baseline timepoint up to 2 years and/or end of treatment

Study Arms (1)

Lenvatinib + Pembrolizumab

EXPERIMENTAL

Participants will take: Lenvatinib - At a pre-determined dose daily during each 3 week study cycle up to 9 cycles Pembrolizumab - 200 mg infusion on Day 1 of each 3 week study cycle up to 35 cycles Participants will be given a drug diary and asked to document information in the drug diary about the study treatment. Participants will be asked to check their blood pressure 3x every week and document in a supplied diary. Participants will be followed up to one (1) year after study treatment.

Drug: Lenvatinib; Drug: Pembrolizumab

Interventions

Lenvatinib DRUG

Pill taken by mouth, once daily.

Also known as: Lenvima

Lenvatinib + Pembrolizumab

Pembrolizumab DRUG

Intravenous injection through a vein (IV).

Also known as: Keytruda

Lenvatinib + Pembrolizumab

Eligibility Criteria

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

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 \>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

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.

Sponsors & Collaborators

• Yale University: lead
• Eisai Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

MeSH Terms

Conditions

Recurrent respiratory papillomatosis; Lung Diseases

Interventions

lenvatinib; pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases

Study Officials

• Sara I Pai, MD, PHD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sara Pai

CONTACT

203-836-0406; sara.pai@yale.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• 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: November 20, 2020
• First Posted: November 27, 2020
• Study Start: July 18, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)