Pembrolizumab + Lenvatinib for Ovarian Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Elizabeth Lee, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Elizabeth K. Lee MD

No Placebo Group

Prior Safety Data

Breakthrough Therapy

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.

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 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 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}

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 am 18 years old or older.

I have had platinum-based chemotherapy for my disease.

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

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.

Treatment Details

Interventions

• Lenvatinib (Tyrosine Kinase Inhibitor)
• Pembrolizumab (Monoclonal Antibodies)

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, 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Dana Farber Cancer Institute Boston, MA

Mayo Clinic Comprehensive Cancer Center Rochester, MN

University of Chicago Medicine Chicago, IL

Who Is Running the Clinical Trial?

Elizabeth K. Lee MD Lead Sponsor

Merck Sharp & Dohme LLC Industry Sponsor

References

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

Combination lenvatinib plus pembrolizumab in the treatment of ovarian clear cell carcinoma: A case series. [2023] Effective second-line treatment options for patients with recurrent ovarian clear cell carcinoma (OCCC) are limited. This case series sought to report tumor characteristics and oncologic outcomes in a small group of patients treated with combination lenvatinib and pembrolizumab. A retrospective analysis of patients with ovarian clear cell carcinoma treated with combination lenvatinib and pembrolizumab at a single institution was performed. Patient and tumor characteristics were collected including demographics and germline/somatic testing. Clinical outcomes were also evaluated and reported. Three patients with recurrent OCCC were included in the study. The median age of patients was 48 years old. All patients had platinum-resistant disease and had received 1-3 prior lines of therapy. The overall response rate was 100% (3/3). Progression-free survival ranged from 10 months to not-yet-reached. One patient remains on treatment, while the other two died of disease with overall survival of 14 and 27 months. Combination lenvatinib-pembrolizumab demonstrated favorable clinical response in these patients with platinum-resistant, recurrent, ovarian clear cell carcinoma.

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] Lenvatinib is a multikinase inhibitor of VEGFR1, VEGFR2, and VEGFR3, and other receptor tyrosine kinases. Pembrolizumab, an antibody targeting PD-1, has moderate efficacy in biomarker-unselected endometrial cancer. We aimed to assess the combination of lenvatinib plus pembrolizumab in patients with advanced endometrial carcinoma, after establishing the maximum tolerated dose in a phase 1b study.

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] To evaluate adverse events (AEs) of combination lenvatinib plus pembrolizumab for the treatment of recurrent endometrial cancer (EC) and to assess outcomes by lenvatinib starting dose.

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] The combination of pembrolizumab, an anti-PD-1 antibody, and lenvatinib, an antiangiogenic multikinase inhibitor, shows synergistic activity in preclinical and clinical studies in solid tumours. We assessed the clinical activity of this combination therapy in patients with pleural mesothelioma who progressed after platinum-pemetrexed chemotherapy.

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022] To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer.

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

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023] The combination of lenvatinib plus pembrolizumab demonstrated a relevant clinical benefit in patients with endometrial carcinoma. The safety profile was consistent with the established profiles of each drug in monotherapy, with the most frequent adverse events being hypertension, an on-target effect, hypothyroidism, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss.

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

Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab. [2023] Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation.

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] To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)-expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial.

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] Pembrolizumab plus lenvatinib is a novel combination with promising efficacy in patients with advanced and recurrent endometrial cancer. This combination demonstrated high objective response rates in a single-arm phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with advanced endometrial cancer (KEYNOTE-146/Study 111) after ≤2 previous lines of therapy. In a randomized phase 3 trial of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer (KEYNOTE-775/Study 309), after 1‒2 previous lines of therapy (including neoadjuvant/adjuvant), this combination improved objective response rates, progression-free survival, and overall survival compared with chemotherapy.