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

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to gather information about an investigational drug combination, Lenvatinib in combination with pembrolizumab, that may help to treat cervical cancers. In this study, we are looking to see whether the combination of lenvatinib and pembrolizumab has any effect on slowing tumor growth in cervical cancer tumors.

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.

What data supports the effectiveness of the drug combination Lenvatinib and Pembrolizumab for cervical cancer?

Research shows that the combination of Lenvatinib and Pembrolizumab has been effective in treating other types of cancer, like endometrial cancer, by improving response rates and survival compared to chemotherapy. This suggests it might also be beneficial for cervical cancer. ^{1 2 3 4 5}

Is the combination of Lenvatinib and Pembrolizumab generally safe for humans?

The combination of Lenvatinib and Pembrolizumab has been studied in patients with endometrial cancer, showing a safety profile consistent with each drug used alone. Common side effects include high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss. ^{1 6 7 8 9}

How is the drug combination of lenvatinib and pembrolizumab unique for treating cervical cancer?

The combination of lenvatinib and pembrolizumab is unique because it pairs a multikinase inhibitor (lenvatinib) with an immune checkpoint inhibitor (pembrolizumab), which has shown promising results in other cancers like endometrial cancer. This approach targets cancer growth and helps the immune system fight cancer cells, offering a novel treatment option compared to traditional chemotherapy. ^{1 3 5 6 10}

Research Team

Jayanthi Lea, MD

Principal Investigator

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

Eligibility Criteria

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

I have had radiation therapy, but it's not considered a previous treatment.

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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]

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 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 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]

References

1. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced or recurrent uterine carcinosarcoma. [2022]

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. Switzerland 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. [2023]

5. England 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. [2022]

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

Toxicity and efficacy of the combination of pembrolizumab with recommended or reduced starting doses of lenvatinib for treatment of recurrent endometrial cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions in Patients with Advanced Endometrial Carcinoma Treated with Lenvatinib Plus Pembrolizumab. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. [2022]