Lenvatinib + Pembrolizumab for Endometrial Cancer

Overseen By Massey Gyn Onc Team

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Virginia Commonwealth University

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS metastases, Heart failure, 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: 8

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining lenvatinib (a cancer medication) and pembrolizumab (an immunotherapy drug) for treating endometrial cancer specifically in Black participants. The goal is to determine if these medications can control the disease when it has progressed despite other treatments. The trial seeks individuals who identify as Black and have certain types of endometrial cancer that have not responded well to previous treatments, particularly if they have tried up to two different therapies. Participants should also be able to swallow pills and have measurable disease on scans. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to adjust your treatment, as these are generally not allowed within 7 days prior to starting the study treatment, except for low-dose steroids.

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

Studies have shown that using lenvatinib and pembrolizumab together can be effective, but some risks exist. Research indicates that about 78% of patients experienced serious side effects with this combination. The most common severe side effects included high blood pressure, low red blood cell count (anemia), weight loss, tiredness, and low platelet count, which can affect blood clotting.

While these side effects are serious, it is important to note that these treatments have approval for other uses, providing some understanding of their safety. However, these treatments can affect individuals differently. Always consult a healthcare provider about the potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Lenvatinib and Pembrolizumab for endometrial cancer because they offer a fresh approach compared to traditional treatments like surgery, radiation, or chemotherapy. Lenvatinib, a targeted therapy, works by inhibiting proteins that promote cancer cell growth, while Pembrolizumab is an immunotherapy that empowers the immune system to detect and destroy cancer cells more effectively. This combination has the potential to tackle cancer from two different angles, offering hope for improved outcomes where standard treatments might fall short.

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

Research has shown that using lenvatinib and pembrolizumab together effectively treats advanced endometrial cancer. Studies have found that this combination helps patients live longer without cancer progression compared to traditional chemotherapy. Specifically, patients experienced a median time of 7.2 months without cancer progression and lived for an average of 18.3 months overall. This treatment also improved cancer response rates compared to chemotherapy. These encouraging results make this combination a strong candidate for further study, particularly in specific groups like Black participants in this trial. Participants in this trial will receive the combination of lenvatinib and pembrolizumab to further evaluate its effectiveness. ^{2 3 6 7 8}

Who Is on the Research Team?

Chelsea Salyer, MD

Principal Investigator

Massey Cancer Center

Are You a Good Fit for This Trial?

This trial is for Black individuals with recurrent endometrial cancer that's mismatch repair-proficient. Participants must have received no more than two prior therapies (excluding maintenance and hormonal treatments), be postmenopausal or not of childbearing potential, and agree to contraception if applicable. They should have measurable disease, an ECOG status of 0-2, and be able to take oral meds. Those with treated/stable brain metastases may qualify.

Inclusion Criteria

I can swallow pills.

I have had 2 or fewer previous cancer treatments, not counting maintenance or hormonal therapies.

My cancer in the treated area has grown significantly.

Exclusion Criteria

I have a condition that affects how my body absorbs medication.

I do not have active hepatitis B or C.

My cancer is one of the specific types: carcinosarcoma, leiomyosarcoma, or stromal sarcoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib 20 mg orally daily and pembrolizumab 200 mg IV every 3 weeks

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The study tests the effectiveness of lenvatinib combined with pembrolizumab in Black patients compared to past trials' results leading to FDA approval. It aims to see how well this combination works specifically in a demographic underrepresented in previous studies.

How Is the Trial Designed?

Group I: Pembrolizumab & Lenvatinib Experimental Treatment 2 Interventions

Lenvatinib, 20 mg administered orally (PO) once daily (QD) during each 21-day cycle, and Pembrolizumab, 200 mg administered by intravenous (IV) infusion on day 1 of each 21-day cycle.

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?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Published Research Related to This Trial

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 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]

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 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 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]

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]

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 48 patients with recurrent endometrial cancer treated with pembrolizumab and lenvatinib, the best objective response rate was 23.8%, indicating a lower effectiveness compared to clinical trial results.

The treatment was associated with notable side effects, with 56.2% of patients requiring a dose reduction of lenvatinib and 16.7% discontinuing treatment due to adverse events, highlighting the importance of monitoring for safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. Kim, J., Noh, JJ., Lee, TK., 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]

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

Long term treatment of advanced endometrial cancer with ... The KEYNOTE-775 study reported a median progression-free survival of 7.2 months and overall survival of 18.3 months for patients with ...

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39641902/

The efficacy and safety of lenvatinib plus pembrolizumab in ... The median time to the first lenvatinib dose reduction was 1.5 (0.92-2.3) months in all patients and was significantly shorter in patients aged ...

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

a real world multi-institutional review of practice patterns ... The results demonstrated that combination pembrolizumab and lenvatinib yielded superior progression-free survival (PFS) in patients with pMMR cancers (6.6 vs 3 ...

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

LENVIMA® (lenvatinib) Plus KEYTRUDA® ... In the primary analysis, the median OS was 17.4 months (95% CI, 14.2-19.9) for LENVIMA plus KEYTRUDA versus 12.0 months (95% CI, 10.8-13.3) for ...

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. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825823014749

Adverse events and oncologic outcomes with combination ... The most common grade ≥ 3 adverse events were hypertension, anemia, weight loss, fatigue, and thrombocytopenia.