Pembrolizumab + Lenvatinib for Ovarian Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Active infection, Autoimmune disease, 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: Unknown

Duration: Up to 735 days (35 cycles of 21 days each)

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot clinical trial studies the effect of pembrolizumab and lenvatinib in treating patients with high-grade serous ovarian cancers. Immunotherapy with monoclonal antibodies such as pembrolizumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Lenvatinib is an enzyme inhibitor that may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and lenvatinib may help to control the disease and provide an effective therapeutic option for cancer.

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, it mentions that participants should not have received certain cancer therapies or live vaccines recently, and should not be on high doses of steroids or immunosuppressive therapy. It's best to discuss your specific medications with the trial team.

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}

Is the combination of pembrolizumab and lenvatinib generally safe for humans?

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

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 targets both the immune system and blood vessel growth in tumors, showing promising results in patients with platinum-resistant ovarian clear cell carcinoma, a condition with limited treatment options. ^{1 2 4 5 9}

Research Team

Amir A. Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adult women with high-grade serous ovarian, fallopian tube, or peritoneal cancers that are resistant to platinum-based treatments. Participants must have controlled blood pressure, good physical function (ECOG 0-1), and measurable disease in the peritoneal cavity or lymph nodes. They should not be pregnant and must agree to follow contraceptive guidance.

Inclusion Criteria

My cancer can be measured and is present in my abdomen or lymph nodes near my spine.

Eligible female participants: Not a WOCBP OR a WOCBP who agrees to follow contraceptive guidance

I am a woman aged 18 or older.

Exclusion Criteria

I have an autoimmune disease treated with medication in the last 2 years.

You have mental health or drug addiction issues that could make it difficult for you to follow the study requirements.

I am currently on medication for an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and lenvatinib. Pembrolizumab is administered intravenously on day 1, and lenvatinib is taken orally daily for 21 days. Treatment cycles repeat every 21 days for up to 35 cycles.

Up to 735 days (35 cycles of 21 days each)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs at 30 days post-treatment, every 6 weeks for 1 year, then every 9 weeks thereafter. Patients with confirmed disease progression are followed every 12 weeks.

1 year

Treatment Details

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The trial studies pembrolizumab (an immunotherapy drug) combined with lenvatinib (an enzyme inhibitor) in treating patients. The goal is to see if this combination can help control the cancer by boosting the immune system's response and stopping cancer cell growth.

Participant Groups

Group I: Cohort B (pembrolizumab, lenvatinib) Experimental Treatment 2 Interventions

Beginning cycle 0, patients receive lenvatinib PO QD on days 1-21. Beginning cycle 1, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Cohort A (pembrolizumab, lenvatinib) Experimental Treatment 2 Interventions

Beginning cycle 0, patients receive pembrolizumab IV over 30 minutes on day 1. Beginning cycle 1, patients also receive lenvatinib PO QD on days 1-21. Treatment repeats every 21 days for up to 35 cycles 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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]

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 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]

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

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

8. England pubmed.ncbi.nlm.nih.gov

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

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]