Pembrolizumab + Lenvatinib for Ovarian Cancer

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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the combination of pembrolizumab and lenvatinib in patients with clear cell ovarian cancer that has returned or not responded to treatment. Pembrolizumab boosts the immune system to fight cancer, and lenvatinib blocks proteins that help cancer grow. These medications have been used together for various cancers, showing promising results.

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.

What data supports the idea that Pembrolizumab + Lenvatinib for Ovarian Cancer is an effective drug?

The available research shows that Pembrolizumab + Lenvatinib was tested on three patients with a specific type of ovarian cancer called ovarian clear cell carcinoma. All three patients had cancer that did not respond to previous treatments. The study found that all three patients showed a positive response to the drug combination, with one patient still undergoing treatment and the other two having survived for 14 and 27 months after starting the treatment. This suggests that the drug combination can be effective for this type of ovarian cancer, especially when other treatments have failed. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination of Pembrolizumab and Lenvatinib for ovarian cancer?

A small study showed that the combination of Pembrolizumab and Lenvatinib was effective in treating three patients with a specific type of ovarian cancer (ovarian clear cell carcinoma) that was resistant to other treatments, with all patients showing a positive response. ^{1 2 3 4 5}

What safety data is available for the combination of Pembrolizumab and Lenvatinib in treating ovarian cancer?

The safety profile of the combination of Pembrolizumab and Lenvatinib has been studied primarily in endometrial cancer, showing adverse events consistent with each drug's known effects. Common side effects include hypertension, hypothyroidism, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss. In ovarian cancer, specifically ovarian clear cell carcinoma, a case series reported favorable clinical responses, but detailed safety data specific to ovarian cancer is limited. ^{1 3 6 7 8}

Is the combination of pembrolizumab and lenvatinib safe for humans?

The combination of pembrolizumab and lenvatinib has been studied in patients with endometrial cancer, showing a safety profile similar to each drug used alone. Common side effects include high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, tiredness, and weight loss. ^{1 3 6 7 8}

Is the drug combination of Lenvatinib and Pembrolizumab promising for ovarian cancer?

Yes, the combination of Lenvatinib and Pembrolizumab is promising for ovarian cancer. In a small study, all patients with a specific type of ovarian cancer responded positively to the treatment, showing that it could be effective, especially for those who have not responded to other treatments. ^{1 3 4 5 9}

How is the drug combination of pembrolizumab and lenvatinib unique for treating ovarian cancer?

The combination of pembrolizumab and lenvatinib is unique for treating ovarian cancer because it has shown promising results in patients with platinum-resistant ovarian clear cell carcinoma, a condition with limited treatment options. This drug duo works by combining an immune checkpoint inhibitor (pembrolizumab) with an antiangiogenic agent (lenvatinib), which together can enhance the body's immune response against cancer cells. ^{1 3 4 5 9}

Research Team

Joyce Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Combination lenvatinib plus pembrolizumab in the treatment of ovarian clear cell carcinoma: A case series. [2023]

2. England 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. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. [2023]

4. England 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

9. England 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. [2022]