Lenvatinib + Pembrolizumab for Respiratory Papillomatosis

Recruiting at 1 trial location

Overseen By Sara I Pai, MD, PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

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)

Prior Safety Data This treatment has passed at least one previous human trial

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

10 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination of lenvatinib and pembrolizumab for respiratory papillomatosis?

Lenvatinib and pembrolizumab have shown effectiveness in treating various types of cancers, including endometrial cancer, when used together. This combination is being explored for its potential to work well in other cancers by combining their abilities to block tumor growth and boost the immune system. ^{1 2 3 4 5}

Is the combination of Lenvatinib and Pembrolizumab safe for humans?

The combination of Lenvatinib and Pembrolizumab has been studied in various cancers and is generally considered safe, but it can cause side effects like high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, tiredness, and weight loss. ^{1 2 4 5 6}

How is the drug combination of lenvatinib and pembrolizumab unique for treating respiratory papillomatosis?

The combination of lenvatinib and pembrolizumab is unique because it combines a multikinase inhibitor (lenvatinib) that targets blood vessel growth with an immune checkpoint inhibitor (pembrolizumab) that helps the immune system attack cancer cells. This approach is novel for respiratory papillomatosis, as there are no standard treatments for this condition. ^{1 2 3 4 7}

What is the purpose of this trial?

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

Research Team

Sara I Pai, MD, PHD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Lenvatinib + Pembrolizumab Experimental Treatment 2 Interventions

Participants will take: Lenvatinib - At a pre-determined dose, 1x daily during each 3 week study cycle up to 35 cycles/2 years Pembrolizumab - At a pre-determined dose, 1x on Day 1 of each 3 week study cycle up to 35 cycles/2 years 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

Findings from Research

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Lenvatinib in Management of Solid Tumors. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Combined use of pembrolizumab and lenvatinib: A review. [2023]

3. England 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. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]

7. United States 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. [2023]