Pembrolizumab + Lenvatinib for Advanced Cervical Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Georgetown University

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Active infection, CNS metastases, 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: 13

Duration: up to 2 years

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combining two drugs, pembrolizumab (an immunotherapy drug) and lenvatinib (a targeted therapy), for women with advanced cervical cancer unresponsive to previous treatment. The goal is to determine if these drugs can enhance the immune system's ability to fight cancer. Women with cervical cancer that has spread or worsened after prior therapy may be suitable for this study. Participants should have a tumor sample available for testing and must not have certain infections or medical conditions that could interfere with the trial. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

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 be on certain therapies like systemic steroids or immunosuppressive drugs shortly before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that pembrolizumab and lenvatinib are generally safe for people with advanced cancer. In past studies, this combination was used in patients with advanced cervical and endometrial cancers, showing promising results for both effectiveness and safety.

For instance, one study found that 16.7% of patients with advanced endometrial cancer were still alive after five years, suggesting a benefit from this treatment. Another study demonstrated that it improved both the time patients lived without their cancer worsening and their overall survival compared to traditional chemotherapy.

Real-world data also support pembrolizumab's safety in advanced cervical cancer, with patients generally tolerating the treatment well. While side effects can occur, the safety profile remains generally acceptable. Researchers continue to explore this combination to help those who might not have responded well to other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cervical cancer?

Researchers are excited about pembrolizumab and lenvatinib for advanced cervical cancer because they offer a novel approach compared to traditional treatments like chemotherapy and radiation. Pembrolizumab is an immunotherapy drug, which works by activating the body's immune system to better recognize and attack cancer cells. Lenvatinib, on the other hand, is a targeted therapy that inhibits the growth of new blood vessels that tumors need to grow. This combination leverages both the immune system and targeted anti-cancer pathways, offering hope for improved outcomes in patients who have limited options with standard treatments.

What evidence suggests that this treatment might be an effective treatment for advanced cervical cancer?

Research has shown that using pembrolizumab and lenvatinib together can help treat advanced cervical cancer. In this trial, participants will receive the combination of pembrolizumab with lenvatinib. One study found that this combination helped patients live longer and respond better to treatment compared to standard chemotherapy. Another review highlighted that these two drugs have shown promising results in fighting tumors in various cancers, including cervical cancer. In real-world use, pembrolizumab alone has been safe and effective for advanced cervical cancer, suggesting that adding lenvatinib could enhance its benefits. Overall, early evidence supports the potential effectiveness of this combination therapy. ^{1 6 7 8 9}

Who Is on the Research Team?

Samir Khleif, MD

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

This trial is for women at least 18 years old with advanced cervical cancer that worsened after first-line therapy. They must have measurable disease, provide a tumor tissue sample, and have proper organ function. Women of childbearing potential must agree to contraception guidelines. Exclusions include severe allergies to the drugs tested, recent other treatments or vaccines, certain health conditions like uncontrolled blood pressure or active infections.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Absolute neutrophil count (ANC) ≥1500/µL

My organs are functioning well, tested within the last 28 days.

Exclusion Criteria

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

I do not have serious heart problems like recent heart attacks or severe heart failure.

My brain metastases are stable, and I haven't needed steroids for 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and lenvatinib combination therapy. The treatment is administered in cycles, with each cycle lasting 21 days.

up to 2 years

Day 1 of each cycle (each cycle is 21 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of overall survival and progression-free survival.

up to 2 years

Every 12 weeks after end of treatment

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The trial tests pembrolizumab combined with lenvatinib in patients with advanced cervical cancer who didn't respond well to initial treatment. It's believed this combo could counteract VEGF-mediated immunosuppression and improve patient response.

How Is the Trial Designed?

Group I: Pembrolizumab with Lenvatinib Experimental Treatment 2 Interventions

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?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

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

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 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]

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]

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]

In a study of 108 patients with advanced endometrial carcinoma, the combination of lenvatinib and pembrolizumab resulted in a 38% objective response rate at 24 weeks, with particularly high efficacy (63.6%) in patients with microsatellite instability (MSI)-high tumors.

The treatment demonstrated a median duration of response of 21.2 months and a median overall survival of 16.7 months, while the combination therapy had a manageable safety profile, with 66.9% of patients experiencing grade 3 or 4 treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. Makker, V., Taylor, MH., Aghajanian, C., et al.[2021]

Pembrolizumab is an FDA-approved immune checkpoint inhibitor specifically targeting the PD-1 receptor, showing promise in treating recurrent or metastatic cervical cancer in patients whose tumors express PD-L1.

Clinical studies suggest that pembrolizumab could become a preferred treatment option for advanced cervical cancer, but further research is needed to identify which patients will benefit the most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced cervical cancer: safety and efficacy. De Felice, F., Giudice, E., Bolomini, G., 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]

In a phase II study involving 10 patients with advanced cervical cancer, the combination of atezolizumab and bevacizumab resulted in an objective response rate (ORR) of 0%, indicating that this treatment did not effectively shrink tumors as hoped.

Despite the lack of confirmed responses, the disease control rate was 60%, with a median progression-free survival of 2.9 months and overall survival of 8.9 months, suggesting some patients experienced stable disease, although safety concerns included two high-grade neurologic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer. Friedman, CF., Snyder Charen, A., Zhou, Q., et al.[2021]

In a study of 4 patients with advanced cervical cancer treated with pembrolizumab, all patients tolerated the treatment well, with one patient achieving a remarkable 21-month progression-free survival, indicating potential efficacy of this PD-1 inhibitor.

Biomarker analysis revealed that patients with a combined positive score (CPS) for PD-L1 of ≥1 and specific somatic mutations, such as in PIK3CA, may benefit from pembrolizumab, suggesting that further research into predictive biomarkers could enhance patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer. Ngoi, NYL., Heong, V., Lee, XW., et al.[2020]

Patients with metastatic cervical cancer have a poor prognosis, with a median survival of only 8-13 months, highlighting the need for more effective treatment options beyond traditional chemotherapy, which is mainly palliative.

Recent advancements in understanding the immune response to Human papillomavirus (HPV) and the development of immunotherapies, along with next-generation sequencing for identifying actionable mutations, offer promising new avenues for treatment in cervical cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy and targeted therapy for cervical cancer: an update. Menderes, G., Black, J., Schwab, CL., et al.[2016]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04865887?term=Khleif&viewType=Table&rank=4

Pembrolizumab and Lenvatinib in Advanced Cervical Cancer A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12359185/

Real-world outcomes after pembrolizumab treatment for ... Pembrolizumab is safe and effective for advanced and recurrent cervical cancer in a real-world population. For those with good performance, ...

3. media-us.eisai.com media-us.eisai.com/KEYTRUDA-R-pembrolizumab-Plus-LENVIMA-R-lenvatinib-Combination-Demonstrated-Statistically-Significant-Improvement-in-Overall-Survival-Progression-Free-Survival-and-Objective-Response-Rate-Versus-Chemotherapy-in-Patients-With-Advanced-Endometrial-Cancer-Fo

KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib ... KEYTRUDA plus LENVIMA demonstrated a statistically significant and clinically meaningful improvement in OS, PFS and ORR versus chemotherapy.

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

Combined use of pembrolizumab and lenvatinib: A review Data suggests that combination therapy with pembrolizumab and lenvatinib can be used first line for clear cell renal carcinoma in patients with favorable risk.

5. merck.com merck.com/news/new-data-from-investigational-study-of-lenvima-lenvatinib-and-keytruda-pembrolizumab-combination-in-three-different-tumor-types-presented-at-the-society-for-immunotherapy-of-cancer/

New Data from Investigational Study of LENVIMA® ... The LENVIMA and KEYTRUDA combination demonstrated encouraging anti-tumor activity. These data support further evaluation of the combination.

6. eisai.com eisai.com/news/2025/news202573.html

LENVIMA® (lenvatinib) Plus KEYTRUDA® ... “Five-year follow-up data from the Study 309/KEYNOTE-775 trial show sustained survival benefit in patients treated with pembrolizumab plus ...

7. merck.com merck.com/news/keytruda-pembrolizumab-plus-lenvima-lenvatinib-demonstrates-durable-5-year-survival-benefit-versus-chemotherapy-for-patients-with-advanced-endometrial-carcinoma-following-one-prior-pla/

KEYTRUDA® (pembrolizumab) Plus LENVIMA® ... At five years, KEYTRUDA plus LENVIMA showed a 16.7% overall survival (OS) rate for these patients with mismatch repair proficient (pMMR) advanced ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2108330

Lenvatinib plus Pembrolizumab for Advanced Endometrial ... Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced ...

9. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-01797

Pembrolizumab and Lenvatinib for the Treatment of Locally ... This phase II trial studies how well pembrolizumab and lenvatinib work in treating patients with cervical cancer that has spread to nearby tissue or lymph ...