Lenvatinib + Pembrolizumab for Respiratory Papillomatosis

Recruiting at 1 trial location

Overseen By Carole Ramm

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active infection, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 2 years

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, Lenvatinib (a targeted therapy) and Pembrolizumab (an immunotherapy), to determine their effectiveness in treating recurrent respiratory papillomatosis (RRP), a condition caused by HPV that leads to growths in the airways. The trial focuses on individuals with confirmed HPV-related growths in their trachea, lungs, or larynx who have undergone multiple surgeries for laryngeal disease. Participants will take Lenvatinib daily and receive Pembrolizumab infusions every three weeks, with regular monitoring and follow-ups for up to a year. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received prior systemic anti-cancer therapy within 4 weeks before the study and should not be on chronic systemic steroid therapy exceeding 10 mg daily of prednisone equivalent. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of lenvatinib and pembrolizumab has been tested in people with other types of cancer. These studies indicate that the treatment can be effective, but like most medications, it may cause side effects. Commonly reported issues include fatigue, diarrhea, and high blood pressure. More serious side effects can occur, though they are less common.

Previous patients have demonstrated that this combination is generally well-tolerated, meaning most people can manage the side effects. However, everyone reacts differently to medications. Before joining a trial, participants should discuss the possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for respiratory papillomatosis?

Researchers are excited about the combination of Lenvatinib and Pembrolizumab for treating Respiratory Papillomatosis because it offers a novel approach compared to existing therapies. Unlike standard treatments that primarily focus on surgically removing papillomas, this combination therapy includes Lenvatinib, which inhibits tumor blood vessel growth, and Pembrolizumab, an immunotherapy that boosts the body's immune response to attack the tumors. This dual action has the potential to not only reduce the size and number of lesions but also improve the body's ability to control the disease over time. By targeting both the tumor and the immune system, this treatment could provide a more comprehensive and long-lasting solution for patients.

What evidence suggests that Lenvatinib + Pembrolizumab could be an effective treatment for respiratory papillomatosis?

Studies have shown that combining lenvatinib and pembrolizumab can help treat certain cancers. Earlier research revealed that more patients experienced tumor shrinkage with this combination, and it also extended the time patients lived without their cancer worsening. Specifically, for head and neck squamous cell carcinoma, 36.4% of patients saw their tumors shrink. Another study found that patients taking these drugs together lived for 23.9 months without disease progression. Based on these promising results, the trial will evaluate the combination of lenvatinib and pembrolizumab for treating conditions like recurrent respiratory papillomatosis linked to HPV. ^{1 2 3 4 5}

Who Is on the Research Team?

Sara I Pai, MD, PHD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Adults with HPV-related recurrent respiratory papillomatosis affecting the larynx, trachea, or lungs. Participants must have had multiple surgeries for laryngeal disease and provide recent biopsy samples. They should not be pregnant, agree to contraception use, and have no severe heart issues or uncontrolled blood pressure. Excludes those with certain serious health conditions, recent cancer treatments, or live vaccines.

Inclusion Criteria

I can provide a recent biopsy sample.

I have had 3 or more surgeries in a year to remove larynx lesions.

I agree to use contraception while on this trial.

Exclusion Criteria

I have a history of Hepatitis B or active Hepatitis C.

You had severe allergic reactions to drugs similar to pembrolizumab or lenvatinib in the past.

Your heart's electrical activity stays prolonged for too long.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lenvatinib daily and Pembrolizumab every 3 weeks for up to 2 years

2 years

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The trial is testing a combination of two drugs: Pembrolizumab and Lenvatinib in patients with HPV-associated respiratory growths that keep coming back. The study aims to see how well these drugs work together to treat this condition.

How Is the Trial Designed?

Group I: Lenvatinib + Pembrolizumab Experimental Treatment 2 Interventions

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.

Lenvatinib is already approved in United States, European Union for the following indications:

Approved in United States as Lenvima for:

• Differentiated Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Lenvima for:

• Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Kisplyx for:

• Renal Cell Carcinoma

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase 2 study involving 54 patients with advanced endometrial cancer, the combination of lenvatinib and pembrolizumab resulted in a 39.6% objective response rate at week 24, indicating significant anti-tumor activity.

The treatment was generally well-tolerated, with serious adverse events occurring in 30% of patients, including one treatment-related death; however, the safety profile was consistent with previous studies of the individual drugs, except for a higher incidence of hypothyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Makker, V., Rasco, D., Vogelzang, NJ., et al.[2020]

Combination therapy with pembrolizumab and lenvatinib is effective as a first-line treatment for clear cell renal carcinoma and as a second-line option for recurrent or metastatic endometrial carcinoma, based on data from five completed clinical trials and two ongoing trials.

This non-chemotherapy regimen helps spare patients from prolonged myelosuppression and lowers the risk of infection, making it a safer alternative for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined use of pembrolizumab and lenvatinib: A review. Eisinger, C., Muluneh, B.[2023]

The combination of pembrolizumab and lenvatinib demonstrated significantly higher objective response rates (ORRs) and progression-free survival (mPFS) compared to their individual therapies in solid cancers, with ORRs reaching up to 70% in renal cell carcinoma.

Despite a high incidence of adverse events (68.0% for the combination therapy), the toxicities were manageable and no unexpected safety issues were reported, indicating that the combination therapy is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review. Mo, DC., Luo, PH., Huang, SX., et al.[2021]

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

In a study of 43 patients with recurrent endometrial cancer treated with lenvatinib and pembrolizumab, 84% experienced significant adverse events (AEs), with hypertension and weight loss being the most common.

Patients starting on a reduced dose of lenvatinib (10 mg or 14 mg) had significantly longer progression-free survival compared to those on the standard dose (20 mg), suggesting that dose optimization may improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. Zammarrelli, WA., Ma, W., Espino, K., et al.[2023]

In the phase II LEAP-004 study involving 103 patients with advanced melanoma who had disease progression on PD-1 inhibitors, the combination of lenvatinib and pembrolizumab achieved an objective response rate of 21.4%, indicating its potential effectiveness in this challenging population.

The treatment demonstrated a median progression-free survival of 4.2 months and an overall survival of 14.0 months, with a manageable safety profile, including a 45.6% incidence of grade 3-5 adverse events, primarily hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination. Arance, A., de la Cruz-Merino, L., Petrella, TM., et al.[2023]

Citations

1. withpower.com withpower.com/trial/phase-3-papilloma-11-2021-91df2

Lenvatinib + Pembrolizumab for Respiratory Papillomatosis The combination of pembrolizumab and lenvatinib demonstrated significantly higher objective response rates (ORRs) and progression-free survival (mPFS) compared ...

2. yalemedicine.org yalemedicine.org/clinical-trials/merck-iit-rrp-pembro-and-lenvatibin

A Phase II Study of Lenvatinib in Combination With ... This research study is studying Lenvatinib in combination with Pembrolizumab in people with human papillomavirus (HPV)-associated recurrent respiratory ...

3. medicine.yale.edu medicine.yale.edu/trial/merck-iit-rrp-pembro-and-lenvatibin/

A Phase II Study of Lenvatinib in Combination With ... This research study is studying Lenvatinib in combination with Pembrolizumab in people with human papillomavirus (HPV)-associated recurrent respiratory ...

4. researchgate.net researchgate.net/publication/327460103_A_phase_1b2_trial_of_lenvatinib_plus_pembrolizumab_in_patients_with_squamous_cell_carcinoma_of_the_head_and_neck

A phase 1b/2 trial of lenvatinib plus pembrolizumab in ... ... Phase I study of pembrolizumab plus lenvatinib in patients with HNSCC, showed the ORR of 36.4% [163] . A phase I trial of Bintrafusp ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10540481/

Combined use of pembrolizumab and lenvatinib: A review Progression free survival (PFS) for the lenvatinib/pembrolizumab group was 23.9 months compared to sunitinib which had a PFS of 9.2 months with a hazard ratio ( ...