Pembrolizumab + Lenvatinib for Uterine Cancer

Not currently recruiting at 9 trial locations

Overseen By Maria Rubinstein, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anti-PD-1, VEGF TKI

Disqualifiers: Immunodeficiency, Active 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: 3

Duration: 27 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two drugs, lenvatinib (a targeted therapy) and pembrolizumab (an immunotherapy), effectively treats advanced uterine cancer known as carcinosarcoma. Researchers are also investigating whether certain blood markers can predict the cancer's response to these treatments. This trial suits individuals who have had uterine carcinosarcoma, undergone at least one round of platinum-based chemotherapy, and experienced cancer recurrence or persistence. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that all hormonal therapy for endometrial or ovarian carcinosarcomas be stopped at least one week before starting the study treatment. Other medications, like chemotherapy, must be completed at least three weeks prior. The protocol does not specify other medications, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that the combination of lenvatinib and pembrolizumab is likely to be safe for humans?

Research has shown that the combination of lenvatinib and pembrolizumab has been tested for safety in other types of cancer. Over five years, researchers found no new safety issues. The side effects matched those already known, with no surprises.

For individuals with advanced endometrial cancer, this combination was tested and found to extend survival compared to chemotherapy. This suggests the treatment is generally well-tolerated and is being considered for wider use.

While this doesn't guarantee the same results for uterine carcinosarcoma, the consistent safety data in similar conditions is promising. Patients should always consult their doctor to understand how these findings might relate to their health. ^{1 2 3 4 5}

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

Researchers are excited about the combination of Pembrolizumab and Lenvatinib for treating uterine cancer because it offers a novel approach that could improve outcomes. Most current treatments for uterine cancer involve surgery, radiation, or chemotherapy, which can be harsh and have varying effectiveness. Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, while Lenvatinib is a tyrosine kinase inhibitor that blocks tumor blood vessel growth. This dual mechanism targets the cancer in two ways, potentially leading to more effective and sustained responses. This combination therapy represents a promising strategy, especially for those whose cancer has become resistant to standard treatments.

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

Studies have shown that using lenvatinib and pembrolizumab together can help treat advanced uterine cancers. Research indicates that this combination, which participants in this trial will receive, allows patients to live longer without their cancer worsening compared to those receiving chemotherapy. In patients with advanced endometrial carcinoma, this treatment demonstrated lasting benefits over five years. Specifically, some patients had a 16.7% chance of surviving five years, which is promising. This suggests the treatment could be a strong option for people with advanced uterine carcinosarcoma. ^{1 2 5 6 7}

Who Is on the Research Team?

Vicky Makker, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with advanced uterine carcinosarcoma who've had one platinum-based chemo and up to three systemic therapies. They must have measurable cancer lesions, stable blood pressure, and adequate organ function. Excluded are those with recent investigational drugs, active autoimmune diseases or pneumonitis, other cancers within two years, CNS metastases, significant liver disease or cardiovascular issues.

Inclusion Criteria

I stopped my hormonal therapy for carcinosarcoma at least a week ago.

My cancer is a specific type that affects the uterus or ovaries and has come back or not gone away.

At least 1 measurable target lesion according to RECIST 1.1

Exclusion Criteria

I have an immune system disorder or have been on immune-weakening drugs recently.

My heart's pumping ability is below the normal range.

I have been treated for an autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lenvatinib (20mg once daily orally) in combination with Pembrolizumab (200mg every 3 weeks, intravenously)

27 weeks

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview Researchers are testing the effectiveness of combining Pembrolizumab (an immunotherapy drug) with Lenvatinib (a targeted therapy) in treating advanced uterine carcinosarcoma. The study also aims to identify biomarkers that could predict how well these treatments work against this type of cancer.

How Is the Trial Designed?

Group I: Pembrolizumab With Lenvatinib Experimental Treatment 2 Interventions

Lenvatinib (20mg once daily orally) in combination with Pembrolizumab (200mg every 3 weeks, intravenously)

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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]

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 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 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]

A 53-year-old patient with advanced endometrial cancer developed posterior reversible encephalopathy syndrome (PRES) after receiving the lenvatinib-pembrolizumab combination therapy, highlighting a potential neurological side effect of this treatment.

MRI and lumbar puncture were crucial in diagnosing the condition, emphasizing the need for careful monitoring of neurological symptoms in patients undergoing LEAP therapy to differentiate between drug-related encephalopathy and other causes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Posterior reversible encephalopathy syndrome, an adverse effect of lenvatinib and pembrolizumab combination therapy, in a patient with advanced endometrial cancer. Matsuura, Y., Nishida, H., Kosaka, T., 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]

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 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]

Citations

1. 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 ...

2. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11950743/

Long term treatment of advanced endometrial cancer with ... This case demonstrates sustained response to lenvatinib and pembrolizumab in a case of recurrent, advanced endometrial cancer.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825825009576

a real world multi-institutional review of practice patterns ... This study is aimed to improve understanding of the treatment landscape in recurrent endometrial cancer real-world clinical practices and provide insight into ...

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

LENVIMA® (lenvatinib) Plus KEYTRUDA® ... “These five-year data highlight the durable survival benefit of LENVIMA plus KEYTRUDA in patients with advanced endometrial carcinoma who have ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601704/

Clinical Review - Pembrolizumab in Combination With ... - NCBI The 5-year survival rate for type I endometrial cancer is around 80% to 90%, while the 5-year survival rate for type II endometrial cancer is as low as 20%.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-01326

First-Line Lenvatinib Plus Pembrolizumab Versus ... Lenvatinib plus pembrolizumab (len + pembro) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in previously ...