Lenvatinib + Pembrolizumab for Endometrial Cancer

Recruiting at 211 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Eisai Inc.

Must not be taking: Steroids, Immunosuppressants, VEGF inhibitors, others

Disqualifiers: CNS metastases, Active infection, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 1

Duration: Up to 35 cycles (21-day cycles for pembrolizumab and lenvatinib, 21 or 28-day cycles for physician's choice)

827 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, pembrolizumab and lenvatinib, to determine if they can help people with advanced endometrial cancer live longer without disease progression. Participants will receive either this combination or one of two standard treatments chosen by their doctor. The trial aims to assess if this new combination is more effective than the usual treatments. Suitable candidates for this trial have advanced endometrial cancer that has worsened despite earlier chemotherapy. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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

Research has shown that the combination of lenvatinib and pembrolizumab has been tested for safety in treating advanced endometrial cancer. In these studies, 78% of patients experienced serious side effects. The most common side effects included high blood pressure, low red blood cell count (anemia), weight loss, tiredness, and low platelet count.

Although these side effects can be serious, these treatments may also extend some patients' lives. Prospective participants should discuss these potential risks with their healthcare team to make an informed decision about joining a clinical trial. ^{1 2 3 4 5}

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

Researchers are excited about the combination of lenvatinib and pembrolizumab for endometrial cancer because it offers a unique approach compared to traditional chemotherapy options like doxorubicin and paclitaxel. Lenvatinib is a targeted therapy that blocks proteins involved in tumor growth, while pembrolizumab enhances the immune system's ability to attack cancer cells. This dual action not only targets the cancer directly but also empowers the body’s natural defenses, potentially leading to more effective and long-lasting results. Unlike standard treatments that focus solely on killing cancer cells, this combination provides a comprehensive attack on the cancer, making it a promising option for patients.

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

Research has shown that using lenvatinib and pembrolizumab together, which participants in this trial may receive, can benefit people with advanced endometrial cancer. One study found that this combination increased the average survival time to 17.4 months, compared to 12.0 months with standard chemotherapy. Another study showed that patients lived an average of 7.2 months without their cancer worsening when using the combination. Long-term data indicated that 16.7% of patients treated with these drugs were still alive after five years. These results suggest that this combination may offer a significant advantage over traditional treatments, which are also being studied in this trial as part of the treatment of physician's choice arm. ^{1 4 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Eisai Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced endometrial cancer who've had one prior platinum-based chemotherapy. They must not be pregnant or breastfeeding and agree to use contraception. Excluded are those with certain other cancers, heart conditions, active infections, HIV/Hepatitis B/C, recent major surgery complications, autoimmune diseases requiring treatment in the past 2 years, or previous treatments that overlap with the study drugs.

Inclusion Criteria

My cancer progressed after 1 platinum-based treatment.

I have a tumor that can be measured and has been confirmed by a review.

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

Exclusion Criteria

My cancer is a specific type affecting the uterus.

I have received an organ or tissue transplant from another person.

I have had more than one chemotherapy treatment for endometrial cancer, but no more than two that included platinum.

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 or treatment of physician's choice for advanced endometrial cancer

Up to 35 cycles (21-day cycles for pembrolizumab and lenvatinib, 21 or 28-day cycles for physician's choice)

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years and 5 months

Post-treatment visit

What Are the Treatments Tested in This Trial?

Interventions

• Doxorubicin
• Lenvatinib
• Paclitaxel
• Pembrolizumab

Trial Overview The trial tests pembrolizumab combined with lenvatinib against a physician's choice of doxorubicin or paclitaxel in treating advanced endometrial cancer. The goal is to see if the combination improves survival without disease progression compared to standard treatments.

How Is the Trial Designed?

Group I: Lenvatinib 20 mg + Pembrolizumab 200 mg Experimental Treatment 2 Interventions

Participants will receive pembrolizumab 200 milligram (mg) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle plus lenvatinib 20 mg administered orally (PO) once daily (QD) during each 21-day cycle for up to 35 cycles.

Group II: Treatment of Physician's Choice Active Control 2 Interventions

Participants will receive either of the following treatments: doxorubicin 60 milligram per square meter (mg/m\^2) administered by IV on Day 1 of each 21-day cycle for up to a maximum cumulative dose of 500 mg/m\^2 OR paclitaxel 80 mg/m\^2 administered by IV on a 28-day cycle: 3 weeks receiving paclitaxel once a week and 1 week not receiving paclitaxel.

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?

Eisai Inc.

Lead Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

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

Citations

1. 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 ...

2. 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 ...

3. 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 ...

4. 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 ...

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 ...

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

The efficacy and safety of lenvatinib plus pembrolizumab in ... Grade ˃3 adverse events (AEs) occurred in 78% of patients who received the lenvatinib + pembrolizumab regimen. AEs resulted in lenvatinib dose ...

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 ...

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.