Triple-Drug Combo for Ovarian Cancer

Not currently recruiting at 1 trial location

Overseen By Callan Myerscough

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Floor Backes, MD

Must not be taking: Antiretrovirals, Immunosuppressants

Disqualifiers: Active CNS metastases, Severe hypersensitivity, Autoimmune disease, Hepatitis, HIV, 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: 3

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of three drugs—lenvatinib, pembrolizumab, and paclitaxel—to treat certain cancers that have returned after treatment. It focuses on endometrial and ovarian cancers, including those affecting the fallopian tubes and peritoneum, which resist standard platinum-based treatments. The trial aims to determine how well these drugs work together and identify potential side effects. Women with ovarian or endometrial cancer that has recurred and does not respond to platinum treatments might be suitable for this study. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received certain cancer treatments or investigational drugs within a specific time frame before starting the trial. It's best to discuss your current medications with the trial team to understand any potential interactions.

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

Research has shown that using lenvatinib and pembrolizumab together holds promise for treating advanced ovarian cancer. One study found that these two drugs can effectively combat the cancer, with no unexpected safety issues reported.

Another study examined pembrolizumab and lenvatinib and found positive effects on cancer, with some patients responding well. This suggests that adding paclitaxel should not introduce new safety problems, as both two-drug combinations have demonstrated safety.

All three drugs—lenvatinib, pembrolizumab, and paclitaxel—have FDA approval for treating other cancers, indicating they have been tested and are generally safe. However, using them together in this trial is new, so researchers continue to study their combined effects and potential side effects. ^{1 2 3 4 5}

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

Researchers are excited about this triple-drug combo for ovarian cancer because it combines three powerful treatments: lenvatinib, paclitaxel, and pembrolizumab. Unlike standard treatments that typically focus on chemotherapy alone, this combo also includes pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells. Additionally, lenvatinib, a targeted therapy, works by inhibiting proteins that promote tumor growth. This multifaceted approach aims to tackle cancer from different angles, offering hope for improved outcomes compared to existing options.

What evidence suggests that this triple-drug combination could be effective for recurrent ovarian cancer?

Research has shown that using lenvatinib and pembrolizumab together holds promise for treating advanced ovarian cancer. One study demonstrated that this combination helped shrink tumors in patients. Another study found that nine patients had a confirmed positive response, suggesting the treatment could be effective. While single immune therapies have not been very successful for ovarian cancer, combining them with other drugs appears beneficial. In this trial, participants will receive a combination of lenvatinib, pembrolizumab, and paclitaxel to determine if adding paclitaxel enhances the treatment's effectiveness. ^{2 3 4 6 7}

Who Is on the Research Team?

Floor Backes, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for women at least 18 years old with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal cancer who have had platinum-based treatment. They must not be pregnant or breastfeeding and should have an acceptable organ function. Prior treatments are allowed under certain conditions but no recent severe side effects from similar drugs.

Inclusion Criteria

My ovarian, fallopian tube, or peritoneal cancer is resistant to platinum-based treatments.

Your hemoglobin level is at least 9.0 g/dL or 5.6 mmol/L within the last 10 days before starting the study treatment.

Your kidney function should be measured according to the hospital's usual method.

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

I have had a bowel blockage or currently have a partial blockage or a PEG-tube.

I have had pneumonitis treated with steroids or have it now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib, pembrolizumab, and paclitaxel. Lenvatinib is taken orally daily, pembrolizumab is administered intravenously on day 1, and paclitaxel is administered intravenously on days 1, 8, and 15 of a 21-day cycle.

Up to 2 years

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests a combination of three FDA-approved drugs: Lenvatinib, Pembrolizumab, and Paclitaxel in patients with specific recurrent cancers. The goal is to determine the effectiveness and safety of this triple-drug regimen which has not been studied before.

How Is the Trial Designed?

Group I: Treatment (paclitaxel, lenvatinib, pembrolizumab) Experimental Treatment 3 Interventions

Patients receive paclitaxel IV over 1 hour on days -15 and -8 and lenvatinib PO QD on days -15 to 0. Beginning cycle 1 day 1, patients receive lenvatinib PO QD, pembrolizumab IV over 30 minutes on day 1, and paclitaxel IV over 1 hour on days 1, 8, and 15. Cycles with pembrolizumab repeats every 3 weeks for up to 2 years, and cycles with paclitaxel and lenvatinib repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

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?

Floor Backes, MD

Lead Sponsor

Trials

2

Recruited

40+

Floor Backes

Lead Sponsor

Trials

3

Recruited

70+

Published Research Related to This Trial

The combination of platinum and paclitaxel has been established as the standard treatment for advanced ovarian cancer since the late 1990s, with further studies suggesting that adding noncross-resistant drugs like epirubicin may enhance treatment efficacy.

In a phase III trial involving 1281 patients, 87% completed six cycles of treatment, providing valuable data on treatment response and toxicity, which will help assess the effectiveness of the new combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The integration of anthracyclines in the treatment of advanced ovarian cancer. Lück, HJ., Du Bois, A., Weber, B., et al.[2018]

The combination of navicixizumab and paclitaxel demonstrated lasting effectiveness in treating patients with platinum-resistant ovarian cancer, indicating a potential new treatment strategy.

This finding suggests that navicixizumab may enhance the therapeutic impact of paclitaxel in a challenging patient population, although specific details on the number of subjects and study duration were not provided.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Navicixizumab plus Paclitaxel Shows Clinical Benefit in Platinum-Resistant Ovarian Cancer. [2022]

Research is focusing on non-cross-resistant drugs like oxaliplatin and topotecan for treating drug-resistant ovarian cancer, with many being tested in combination therapies to improve outcomes.

Innovative strategies such as anticancer vaccines and gene therapy are being explored, highlighting the importance of clinical trials for women with advanced ovarian cancer due to low current cure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative therapies for advanced ovarian cancer. Trimble, EL.[2012]

A platinum/taxane combination is identified as the optimal treatment backbone for chemonaive ovarian cancer based on trials from the Gynecologic Oncology Group over the past 15 years.

Adding a third drug to this combination is unlikely to significantly improve outcomes; however, using sequential doublets of drugs like cisplatin with gemcitabine or topotecan with doxil or etoposide may enhance treatment efficacy due to their complementary mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Gynecologic Oncology Group experience in ovarian cancer. McGuire, WP., Brady, MF., Ozols, RF.[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]

Docetaxel has shown comparable effectiveness to paclitaxel when combined with carboplatin for treating advanced ovarian cancer, with a potentially better safety profile.

Current treatments for platinum-resistant ovarian cancer are limited, and while some experimental therapies targeting the epidermal growth factor receptor show promise, more research is needed to find effective new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. Costa, SD., von Minckwitz, G., Wernicke, K., et al.[2008]

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 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 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]

In a phase Ib study involving 44 patients with platinum-resistant ovarian cancer, the combination of navicixizumab and paclitaxel showed a promising overall objective response rate of 43.2%, indicating its potential efficacy in treating this difficult-to-treat cancer.

The treatment was well-tolerated, with no dose-limiting toxicities reported, although some patients experienced manageable side effects like hypertension and neutropenia, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer. Fu, S., Corr, BR., Culm-Merdek, K., 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 ... The use of single agent immune checkpoint inhibitors has not shown significant clinical benefit in ovarian cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04781088

Study Details | NCT04781088 | Lenvatinib, Pembrolizumab ... The purpose of this trial is to study how well lenvatinib, pembrolizumab, and weekly paclitaxel work together in women who have recurrent endometrial cancer and ...

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

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

4. sciencedirect.com sciencedirect.com/science/article/pii/S0090825824001963

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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8663341/

Pembrolizumab and lenvatinib versus carboplatin ... We found that first-line therapy for advanced or recurrent endometrial cancer with P/L increased costs and worsened outcomes compared to C/T.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12404960/

Pembrolizumab combined with lenvatinib and metronomic ... Most patients with ovarian cancer experience disease recurrence or progression, and ultimately progress to platinum resistance.

7. merck.com merck.com/news/merck-advances-oncology-innovation-highlighting-progress-in-new-tumor-types-and-earlier-stages-of-disease-at-esmo-2025/

Merck Advances Oncology Innovation, Highlighting ... Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer ... safety data for KEYTRUDA ...