Lenvatinib + Pembrolizumab for Cervical Cancer

Overseen By Annette Paulsen

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Pregnancy, Active infection, Autoimmune, 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: 3

Duration: 104 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two drugs, lenvatinib (a targeted therapy) and pembrolizumab (an immunotherapy), can slow the growth of cervical cancer tumors. It focuses on women whose cervical cancer has recurred or spread. Suitable candidates are women previously treated for advanced cervical cancer, including those who have received up to two different chemotherapy treatments. Participants should also have undergone a PD-L1 diagnostic test on their cancer tissue. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the study team to ensure they don't interfere with the trial treatments.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of lenvatinib and pembrolizumab has been studied in other cancers, with varying levels of safety. In some studies, patients experienced side effects. For example, one review found that 21% of patients had severe side effects when using pembrolizumab alone for cervical cancer. These side effects, known as "adverse events," can range from mild to severe.

When used together, lenvatinib and pembrolizumab have been tested in other cancers, such as advanced endometrial cancer, and have shown promising results for survival. However, side effects remain a concern. It is important to discuss these potential risks and benefits with trial doctors before joining.

Since this trial is in an early phase, the safety of this drug combination is still under careful study. Participants should consider this when deciding to join. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for cervical cancer?

Researchers are excited about the combination of Lenvatinib and Pembrolizumab for cervical cancer because it offers a novel approach compared to traditional treatments like chemotherapy or radiation. Unlike standard therapies, this combination uses a dual mechanism: Pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells, while Lenvatinib inhibits tumor blood vessel growth, cutting off the cancer's supply line. This synergy could potentially enhance effectiveness and provide an option for patients who have not responded well to existing treatments.

What evidence suggests that the combination of lenvatinib and pembrolizumab might be an effective treatment for cervical cancer?

Research has shown that using lenvatinib and pembrolizumab together may effectively treat cervical cancer. One study demonstrated that this combination extended patient survival to an average of 17.4 months, compared to 12.0 months with another treatment. It also prolonged the time patients lived without their cancer worsening. Another study found this treatment particularly beneficial for advanced cancers, showing better results in delaying cancer progression. These findings suggest that participants in this trial receiving lenvatinib and pembrolizumab may experience slowed tumor growth and improved survival. ^{1 3 4 6 7}

Who Is on the Research Team?

Jayanthi Lea, MD

Principal Investigator

Professor and Division Chief, Obstetrics & Gynecology, OB-Gynecologic Oncology

Are You a Good Fit for This Trial?

This trial is for individuals with cervical cancer that has spread (metastatic) or come back (recurrent). Participants should meet certain health standards, but specific inclusion and exclusion criteria are not listed.

Inclusion Criteria

Participants must have the ability to understand and sign a written informed consent

Participants must have a PD-L1 diagnostic test of primary or recurrent archival tumor tissue

Participants must have measurable disease based on RECIST 1.1

Exclusion Criteria

A WOCBP with a positive pregnancy test within 72 hours prior to enrollment

Participants who have received an investigational agent or used an investigational device within 4 weeks prior to study intervention administration

Participants with severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200 mg every 3 weeks and lenvatinib 20 mg daily for up to 2 years

104 weeks

Pembrolizumab administered every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Extension

Participants may receive up to 1 year of additional pembrolizumab and lenvatinib upon disease progression

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview

The study is testing a combination of two drugs, Lenvatinib and Pembrolizumab, to see if they can slow down the growth of tumors in patients with cervical cancer.

How Is the Trial Designed?

Group I: Pembrolizumab and Lenvatinib Arm Experimental Treatment 2 Interventions

Pembrolizumab 200 mg q 3 weeks IV Lenvatinib 20 mg PO QD Continue q3 weeks Pembrolizumab and Lenvatinib will be given together in this trial for a maximum of 2 years i.e. a total of 35 cycles of pembrolizumab with the q3 week dosing and Lenvatinib daily. Participants who complete study intervention after 2 years of pembrolizumab and lenvatinib are eligible for up to 1 year of additional pembrolizumab and lenvatinib (second course) upon experiencing disease progression.

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?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

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 study of 70 patients with recurrent endometrial cancer, a lower starting dose of lenvatinib (14 mg daily) combined with pembrolizumab was found to be safe and effective, showing similar response rates compared to the recommended dose (20 mg).

Patients with carcinosarcoma histology experienced notable clinical benefits, with a response rate of 25% and a clinical benefit rate of 58.3%, indicating that this treatment combination may be particularly effective for this subtype of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of the combination of pembrolizumab with recommended or reduced starting doses of lenvatinib for treatment of recurrent endometrial cancer. How, JA., Patel, S., Fellman, B., et al.[2022]

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]

The combination of lenvatinib and pembrolizumab significantly improved treatment outcomes for patients with advanced endometrial cancer compared to chemotherapy, regardless of tumor characteristics, based on data from Study-309/KEYNOTE-775.

Common adverse reactions included hypothyroidism, hypertension, and fatigue, with effective management strategies involving patient education, monitoring, and appropriate dose adjustments to minimize treatment interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab. Colombo, N., Lorusso, D., Monk, BJ., et al.[2023]

The combination of lenvatinib and pembrolizumab is effective for treating advanced endometrial carcinoma, particularly in patients who have not responded to prior therapies, with manageable safety profiles similar to each drug used alone.

Common adverse reactions include hypothyroidism (51% incidence), fatigue, hypertension, and nausea, which typically occur within the first 10 weeks of treatment and can be effectively managed with dose adjustments and supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions in Patients with Advanced Endometrial Carcinoma Treated with Lenvatinib Plus Pembrolizumab. Makker, V., Taylor, MH., Oaknin, A., et al.[2022]

In a phase 1b study involving 6 Japanese patients with metastatic solid tumors, the combination of lenvatinib and pembrolizumab was well-tolerated, with no dose-limiting toxicities reported.

The treatment showed promising antitumor activity, with an objective response rate of 33.3%, particularly in patients with urothelial cancer, indicating potential efficacy for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. Kitano, S., Fujiwara, Y., Shimizu, T., et al.[2022]

In a study of 7 women with advanced or recurrent uterine carcinosarcoma (UCS) treated with pembrolizumab and lenvatinib, the combination therapy showed limited efficacy, with no observed partial or complete responses.

The median progression-free survival (PFS) was only 2.6 months and overall survival (OS) was 2.8 months, suggesting that this treatment may not be more effective than traditional chemotherapy options for UCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced or recurrent uterine carcinosarcoma. Hunt, JT., Chambers, LM., Yao, M., et al.[2022]

In a phase 3 study involving 487 patients with advanced urothelial carcinoma, the combination of pembrolizumab and lenvatinib did not show improved progression-free survival (4.5 months) or overall survival (11.8 months) compared to pembrolizumab with placebo.

The combination treatment resulted in a higher rate of severe adverse events (51%) compared to the placebo group (27%), leading to the conclusion that the benefit-to-risk ratio was not favorable for using lenvatinib with pembrolizumab as first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. Matsubara, N., de Wit, R., Balar, AV., et al.[2023]

The combination of pembrolizumab and lenvatinib has shown promising efficacy in treating advanced endometrial cancer, with previous trials indicating improved objective response rates and survival outcomes compared to standard chemotherapy.

This ongoing phase 3 trial aims to determine if pembrolizumab plus lenvatinib is superior to the chemotherapy regimen of paclitaxel plus carboplatin in newly diagnosed patients, with a target enrollment of about 875 participants and results expected in 2022.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. Marth, C., Tarnawski, R., Tyulyandina, A., et al.[2022]

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 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]

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