Pembrolizumab + Lenvatinib for Ovarian Cancer

Not currently recruiting at 2 trial locations

Overseen By DFCI Clinical Trials Hotline

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Joyce Liu, MD

Must not be taking: Immunosuppressants, Herbal supplements

Disqualifiers: HIV, Hepatitis B, Cardiovascular impairment, 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: 9

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of combining two drugs, pembrolizumab (an immunotherapy) and lenvatinib (a targeted therapy), to treat clear cell ovarian cancer. Researchers aim to determine if this drug combination can better manage the disease. It suits those diagnosed with clear cell ovarian cancer that has recurred or persists after at least one round of platinum-based chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you must stop any immunosuppressive therapy, including high-dose steroids, at least 2 weeks before starting the study. Herbal supplements must be stopped at least 1 week prior. If you're on antihypertensive medications, they should be stable for 2 weeks before the trial. Consult with the trial team for guidance on other medications.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop using herbal supplements at least 1 week before starting the study. If you are on immunosuppressive therapy or have had recent anti-cancer treatments, there are specific timeframes you need to follow before joining the trial.

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

Research has shown that using pembrolizumab and lenvatinib together is generally safe for treating certain types of ovarian cancer. In studies involving patients with advanced ovarian cancer, this combination revealed no unexpected safety issues. Some patients experienced side effects, but these were often manageable; for instance, reducing the dose of lenvatinib helped lessen these effects.

One study found that this combination had a 37.5% response rate in patients with a specific type of ovarian cancer that didn't respond to other treatments. More than a third of these patients saw their cancer shrink or stop growing.

While these findings are promising, side effects can still occur. Some people may feel tired, have high blood pressure, or experience other symptoms. Always discuss any concerns with a doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pembrolizumab and Lenvatinib for treating ovarian cancer because it offers a unique approach compared to traditional therapies. While most current treatments focus on chemotherapy, Pembrolizumab works by enhancing the immune system's ability to recognize and attack cancer cells, acting as an immune checkpoint inhibitor. Lenvatinib, on the other hand, inhibits the growth of blood vessels that supply tumors, acting as a tyrosine kinase inhibitor. This dual mechanism not only targets cancer cells directly but also disrupts their supportive environment, potentially making it more effective than existing options.

What evidence suggests that pembrolizumab and lenvatinib might be an effective treatment for ovarian cancer?

Research has shown that using pembrolizumab and lenvatinib together may hold promise for treating ovarian cancer. In earlier studies, about 35-37.5% of patients with difficult-to-treat ovarian cancer, such as those not responding to platinum-based treatments, experienced tumor shrinkage. In this trial, participants will receive a combination of pembrolizumab, which helps the immune system attack cancer cells, and lenvatinib, which cuts off the blood supply to tumors. Together, they combat cancer in different ways. These findings suggest that this combination could benefit patients with clear cell ovarian cancer. ^{5 6 7 8 9}

Who Is on the Research Team?

Joyce Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with recurrent or persistent clear cell ovarian cancer who've had at least one platinum-based chemotherapy. They must have measurable disease, stable health status (ECOG 0 or 1), adequate organ function, controlled blood pressure, and no major recent surgeries. Women of childbearing age need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

I have had platinum-based chemotherapy for my disease.

I have had multiple treatments for my recurring or persistent disease.

I have previously been treated with bevacizumab.

Exclusion Criteria

Is known to be positive for Human Immunodeficiency Virus (HIV)

My cancer has spread to my intestines.

I will stop taking herbal supplements at least 1 week before starting the study treatment.

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 until progression of disease or unacceptable toxicity

Up to 3 years

Evaluations every 3 cycles (each cycle is 3 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Follow-up every 6 months (off due to PD) or every 3 months (off not due to PD)

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The study tests the combination of pembrolizumab and lenvatinib in treating clear cell ovarian cancer. It aims to determine how safe and effective this drug duo is when given together to patients who meet specific health criteria.

How Is the Trial Designed?

Group I: PEMBROLIZUMAB and LENVATINIB Experimental Treatment 2 Interventions

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. The names of the study drugs involved in this study are: * Lenvatinib * Pembrolizumab Treatment will continue until progression of disease or unacceptable toxicity. Participants will be followed for up to 36 months after discontinuation of study treatment.

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?

Joyce Liu, MD

Lead Sponsor

Trials

1

Recruited

30+

Elizabeth K. Lee MD

Lead Sponsor

Trials

1

Recruited

30+

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 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 Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

In a small case series of three patients with recurrent ovarian clear cell carcinoma (OCCC), the combination of lenvatinib and pembrolizumab resulted in a remarkable overall response rate of 100%.

Patients experienced progression-free survival ranging from 10 months to not-yet-reached, indicating that this treatment may be effective for those with platinum-resistant disease, although two patients ultimately succumbed to their illness after 14 and 27 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination lenvatinib plus pembrolizumab in the treatment of ovarian clear cell carcinoma: A case series. Calo, CA., Levine, MD., Brown, MD., 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]

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 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 2 study involving 38 patients with pleural mesothelioma, the combination of pembrolizumab and lenvatinib resulted in a promising objective response rate of 58%, indicating significant anti-tumor activity after prior chemotherapy.

However, the treatment was associated with considerable toxicity, with 26% of patients experiencing serious treatment-related adverse events, including one death, highlighting the need for careful monitoring and supportive care during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study. Douma, LH., Lalezari, F., van der Noort, V., et al.[2023]

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12309482/

Pembrolizumab and lenvatinib in the treatment of recurrent ... Advanced stage ovarian carcinoma has a poor prognosis with recurrence rates of over 80%, 5-year survival of 36–45%, and limited response to ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e17612

Pembrolizumab and lenvatinib in the treatment of recurrent ... At the time of data analysis, 2 patients remained on treatment. Conclusions: Pembrolizumab-lenvatinib therapy demonstrated favorable clinical ...

3. onclive.com onclive.com/view/pembrolizumab-plus-lenvatinib-elicits-clinically-meaningful-responses-in-platinum-resistant-hgsoc

Pembrolizumab Plus Lenvatinib Elicits Clinically ... Pembrolizumab and lenvatinib showed a 37.5% overall response rate in platinum-resistant high-grade serous ovarian cancer, with partial responses ...

4. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(24)00196-3/fulltext

Results from the phase 2 multicohort LEAP-005 study Lenvatinib plus pembrolizumab had an objective response rate of 35% by blinded independent central review in this population.

5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2829929

Pembrolizumab in Patients With Advanced Clear Cell ... Pembrolizumab showed clinical benefit in patients with previously treated advanced CCGC, warranting further evaluation in a randomized clinical trial.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5515

A phase II trial of pembrolizumab and lenvatinib in ... Conclusions: The combination of pembrolizumab/lenvatinib demonstrates encouraging evidence of clinical activity in CCOC, with 9 pts experiencing ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2352578925001365

Pembrolizumab and lenvatinib in the treatment of recurrent ... Pembrolizumab/lenvatinib is a safe, effective option for treatment of platinum resistant ovarian cancer. Reduced doses of lenvatinib may help mitigate toxicity ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38718741/

Results from the phase 2 multicohort LEAP-005 study Lenvatinib plus pembrolizumab demonstrated antitumor activity as fourth line therapy in patients with advanced ovarian cancer, and no unanticipated safety ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05296512

Pembrolizumab and Lenvatinib in Clear Cell Ovarian Cancer This research study is being done to test the efficacy and safety of combining the study drugs pembrolizumab and lenvatinib in patients with clear cell ovarian ...