Pembrolizumab + Lenvatinib for Endometrial Cancer

(LEAP-001 Trial)

No longer recruiting at 239 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Corticosteroids, Chemotherapy, others

Disqualifiers: CNS metastasis, Cardiovascular disease, Autoimmune, 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: 3

Duration: Up to approximately 44 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new combination of drugs, pembrolizumab (an immunotherapy drug) and lenvatinib (a targeted therapy), is more effective than standard chemotherapy for women with advanced or recurring endometrial cancer. Researchers seek to discover if these drugs can extend patients' lives without worsening the cancer. Women with Stage III, IV, or recurrent endometrial cancer, who may have previously undergone treatments like chemotherapy with radiation, could be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to potentially groundbreaking treatment.

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, if you are on certain treatments like systemic chemotherapy, hormonal therapy, or immunosuppressive drugs, you may need to stop them before joining the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that pembrolizumab and lenvatinib are likely to be safe for humans?

Research has shown that the combination of lenvatinib and pembrolizumab was tested for safety in patients with advanced endometrial cancer. In these studies, 78% of patients experienced serious side effects, prompting doctors to adjust the lenvatinib dose for some patients.

Both lenvatinib and pembrolizumab have received FDA approval for other uses, indicating thorough safety testing in different contexts.

Prospective trial participants should discuss potential risks and their implications with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of pembrolizumab and lenvatinib for endometrial cancer because it introduces a novel approach by pairing an immunotherapy with a targeted therapy. Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, while lenvatinib targets proteins involved in cancer cell growth and blood vessel development, cutting off the tumor's blood supply. This dual action is different from standard treatments like paclitaxel and carboplatin, which are traditional chemotherapy agents that kill rapidly dividing cells. By combining these mechanisms, the hope is to improve outcomes for patients with endometrial cancer beyond what's currently possible with existing therapies.

What evidence suggests that pembrolizumab + lenvatinib could be an effective treatment for endometrial cancer?

In this trial, participants will receive either the combination of pembrolizumab and lenvatinib or the combination of paclitaxel and carboplatin. Research has shown that using pembrolizumab and lenvatinib together yields promising results for treating advanced endometrial cancer. One study found that this combination helped patients live longer without their cancer progressing and increased their overall survival time compared to chemotherapy. Specifically, patients lived for an average of 7.2 months without their cancer worsening and had an overall survival time of 18.3 months. Additionally, more patients experienced tumor shrinkage or disappearance with pembrolizumab and lenvatinib than with chemotherapy. These findings suggest that this treatment could be more effective than traditional chemotherapy for endometrial cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for women with advanced (Stage III or IV) or recurrent endometrial carcinoma. Participants must have a performance status indicating they can carry out daily activities with little to no assistance, controlled blood pressure, and adequate organ function. They should not be pregnant or breastfeeding and agree to use contraception if of childbearing potential.

Inclusion Criteria

I have provided a sample of my tumor for MMR status testing.

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

I have advanced or recurrent endometrial cancer that can be seen on scans.

Exclusion Criteria

Has known intolerance to study intervention (or any of the excipients)

I have a severe fistula.

Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either pembrolizumab plus lenvatinib or chemotherapy for endometrial carcinoma

Up to approximately 44 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 51 months

Open-label extension (optional)

Eligible participants may continue to receive pembrolizumab monotherapy, lenvatinib monotherapy, or a combination of both

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The study tests the effectiveness of pembrolizumab plus lenvatinib against standard chemotherapy in improving survival without cancer progression. It's designed to see if this combination works better than chemotherapy alone for patients with certain stages of endometrial cancer.

How Is the Trial Designed?

Group I: Lenvatinib + Pembrolizumab Experimental Treatment 2 Interventions

Participants receive lenvatinib daily and pembrolizumab once at the start of each 3-week treatment cycle.

Group II: Paclitaxel + Carboplatin Active Control 2 Interventions

Participants receive paclitaxel and carboplatin once at the start of each 3-week treatment 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?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead 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

Eisai Inc.

Industry 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

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39504640/

Real World Outcomes in Patients With Recurrent, ... This real-world, observational study of pem/len showed comparable tolerability, toxicity, and outcomes to previously reported clinical trial ...

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. 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 ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603321/

Pembrolizumab (Keytruda) in Combination With Lenvatinib ... Treatment with PEM-LEN also showed a statistically significant and clinically meaningful improvement in objective response rate (ORR) (ORR = 30.3% and 15.1% ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2352578925000426

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 endometrial cancer on ...

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. 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 ...

8. 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 ...