Lenvatinib + Pembrolizumab for Locally Advanced Kidney Cancer

Overseen By Mehmet A Bilen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Immunosuppressants, Steroids, Biologics, others

Disqualifiers: Metastatic disease, Active infection, 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: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of lenvatinib and pembrolizumab to shrink kidney cancer tumors before surgery. Lenvatinib blocks certain enzymes to stop tumor growth, while pembrolizumab helps the immune system attack cancer cells. The trial targets patients whose kidney cancer has spread to nearby tissues or lymph nodes but not to distant parts of the body. Individuals with renal cell carcinoma, a type of kidney cancer considered not easily removable by surgery, might be suitable for this trial. 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 taking your current medications. However, if you are on anticoagulant therapy, your PT or aPTT must be within the therapeutic range. It's best to discuss your specific medications with the trial team.

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, if you are on anticoagulant therapy, it must be within the therapeutic range. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of lenvatinib and pembrolizumab has been studied for treating kidney cancer. In these studies, patients demonstrated promising results, including a 21% reduction in the risk of death compared to sunitinib. This indicates a potential survival benefit for patients with advanced kidney cancer.

However, safety remains a concern. In real-world settings, some patients required treatment adjustments due to side effects. While the treatment can be effective, it may also cause side effects that necessitate changes. Importantly, recent observations have reported no worsening of cancer, which is encouraging.

This treatment is currently undergoing evaluation in a phase 2 trial to assess safety and effectiveness. Earlier studies suggest it is generally well-tolerated, but individual reactions can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of lenvatinib and pembrolizumab for locally advanced kidney cancer because it offers a novel approach compared to existing treatments. Lenvatinib, a targeted therapy, works by inhibiting proteins that promote tumor growth, while pembrolizumab, an immunotherapy, helps the immune system recognize and attack cancer cells. This combination could potentially enhance the effectiveness of treatment by simultaneously targeting tumor growth and boosting the body's immune response, offering hope for improved outcomes compared to the current standard of care, which typically involves either targeted therapy or immunotherapy alone.

What evidence suggests that lenvatinib and pembrolizumab might be effective for kidney cancer?

Research has shown that combining lenvatinib and pembrolizumab effectively treats renal cell carcinoma (RCC), a type of kidney cancer. In this trial, participants will receive this combination. Studies have found that it can significantly lower the risk of death compared to treatments like sunitinib. This therapy stops enzymes that help cancer cells grow and boosts the immune system to fight cancer cells. Additionally, this treatment is already approved for advanced RCC in some regions. These findings suggest promising results for using lenvatinib and pembrolizumab in treating locally advanced kidney cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Mehmet Bilen, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer that hasn't spread beyond nearby tissues or lymph nodes. Participants must have a certain level of physical fitness (ECOG <=1), adequate organ function, and no recent other cancer treatments. They should not be pregnant or breastfeeding and must agree to use effective contraception.

Inclusion Criteria

My liver function tests are within the required limits.

Your kidney function is measured using the Cockcroft and Gault formula.

Your kidney function needs to be checked based on the hospital's method for measuring it.

Exclusion Criteria

I have an active Hepatitis B or C infection.

My HIV is not under control, with a low CD4+ count or recent serious infection.

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib orally once daily and pembrolizumab intravenously every 21 days for up to 4 cycles (12 weeks) before surgery

12 weeks

4 visits (in-person)

Surgery

Participants undergo nephrectomy (partial or radical) after completion of treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits within 14 days post-treatment and every 12 weeks thereafter

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The study tests the combination of Lenvatinib, an enzyme inhibitor, with Pembrolizumab, an immunotherapy drug, before surgery in patients with non-metastatic clear cell renal carcinoma. The goal is to see if this pre-surgery treatment can better eliminate tumor cells.

How Is the Trial Designed?

Group I: Treatment (lenvatinib, pembrolizumab) Experimental Treatment 5 Interventions

Patients receive lenvatinib PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatments repeat every 21 days for up to 4 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?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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

In the KEYNOTE-B61 trial involving 158 patients with advanced non-clear-cell renal cell carcinoma, the combination of pembrolizumab and lenvatinib demonstrated a 49% objective response rate, indicating significant antitumor activity as a first-line treatment.

The safety profile was consistent with previous studies, with 51% of patients experiencing grade 3-4 treatment-related adverse events, primarily hypertension, but no deaths were attributed to the treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. Albiges, L., Gurney, H., Atduev, V., et al.[2023]

Combination therapy with pembrolizumab and lenvatinib is effective as a first-line treatment for clear cell renal carcinoma and as a second-line option for recurrent or metastatic endometrial carcinoma, based on data from five completed clinical trials and two ongoing trials.

This non-chemotherapy regimen helps spare patients from prolonged myelosuppression and lowers the risk of infection, making it a safer alternative for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined use of pembrolizumab and lenvatinib: A review. Eisinger, C., Muluneh, B.[2023]

In a phase 3 trial with 1069 patients, the combination of lenvatinib and pembrolizumab significantly improved progression-free survival compared to sunitinib, with a median of 23.9 months versus 9.2 months, indicating a strong efficacy of this regimen.

Lenvatinib plus pembrolizumab also resulted in longer overall survival compared to sunitinib, while the combination of lenvatinib and everolimus did not show a survival advantage over sunitinib. However, both lenvatinib combinations had a high incidence of grade 3 or higher adverse events, similar to sunitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. Motzer, R., Alekseev, B., Rha, SY., et al.[2022]

In a phase 1b study involving 6 Japanese patients with metastatic solid tumors, the combination of lenvatinib and pembrolizumab was well-tolerated, with no dose-limiting toxicities reported.

The treatment showed promising antitumor activity, with an objective response rate of 33.3%, particularly in patients with urothelial cancer, indicating potential efficacy for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. Kitano, S., Fujiwara, Y., Shimizu, T., 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 3 study involving 1069 patients with advanced renal cell carcinoma, the combination of lenvatinib and pembrolizumab showed similar or better health-related quality of life (HRQOL) outcomes compared to sunitinib, particularly in terms of time to definitive deterioration.

Patients receiving lenvatinib plus pembrolizumab experienced longer median times to deterioration in quality of life measures, indicating that this combination therapy not only improves survival but also maintains a better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life outcomes in patients with advanced renal cell carcinoma treated with lenvatinib plus pembrolizumab or everolimus versus sunitinib (CLEAR): a randomised, phase 3 study. Motzer, R., Porta, C., Alekseev, B., et al.[2023]

In the CLEAR study involving 352 patients, the combination of lenvatinib and pembrolizumab showed a manageable safety profile, with common adverse reactions including fatigue (63.1%), diarrhea (61.9%), and hypertension (56.3%).

Most adverse reactions occurred within approximately 5 months of starting treatment, and effective management strategies such as monitoring and dose modifications were identified to ensure patient safety and support ongoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. Motzer, R., George, S., Merchan, JR., et al.[2023]

The combination of lenvatinib and pembrolizumab demonstrated promising antitumor activity in patients with metastatic renal cell carcinoma (RCC), with an objective response rate of 72.7% in treatment-naive patients and 55.8% in those previously treated with immune checkpoint inhibitors, based on a study of 143 patients.

While the treatment showed efficacy, it also had a manageable safety profile, with 57% of patients experiencing grade 3 treatment-related adverse events, primarily hypertension, and 7% experiencing grade 4 events, indicating that careful monitoring is necessary during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study. Lee, CH., Shah, AY., Rasco, D., et al.[2022]

In a subset analysis of the CLEAR study involving 73 Japanese patients with advanced renal cell carcinoma, the combination of lenvatinib and pembrolizumab showed significantly longer progression-free survival (22.1 months) compared to sunitinib (10.9 months).

The combination therapy also resulted in a higher objective response rate (69.0% vs. 45.2%) and longer median duration of response (20.3 months vs. 9.1 months), although it was associated with a higher incidence of grade ≥3 treatment-emergent adverse events (95.2% vs. 87.1%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab versus sunitinib for advanced renal cell carcinoma: Japanese patients from the CLEAR study. Eto, M., Takagi, T., Kimura, G., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2949820125000311

Effectiveness, toxicity and treatment adjustments of ... Lenvatinib plus pembrolizumab is effective in RCC outside of clinical trials. A large subset of patients required treatment adjustments due to AEs.

2. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-kidney-cancer/164170-esmo-2025-final-analysis-of-lenvatinib-pembrolizumab-versus-sunitinib-in-patients-with-advanced-rcc-with-or-without-bone-metastases-in-clear.html

ESMO 2025: Final Analysis of Lenvatinib + Pembrolizumab ... Lenvatinib in combination with the anti-programmed death-1 therapy pembrolizumab showed statistically significant/clinically meaningful ...

3. merck.com merck.com/news/keytruda-pembrolizumab-plus-lenvima-lenvatinib-demonstrates-long-term-durable-survival-benefit-versus-sunitinib-as-first-line-treatment-for-patients-with-advanced-renal-cell-carcinoma/

KEYTRUDA® (pembrolizumab) Plus LENVIMA® ... After four years of follow-up, KEYTRUDA plus LENVIMA reduced the risk of death by 21% versus sunitinib in the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 ...

4. eisai.com eisai.com/news/2022/news202210.html

LENVIMA®（LENVATINIB）IN COMBINATION WITH ... This marks the first approval for LENVIMA which will be used in combination with KEYTRUDA for advanced RCC in Asia.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04393350

Study Details | NCT04393350 | Perioperative Lenvatinib ... This phase II trial studies how well lenvatinib and pembrolizumab before surgery work in treating patients with kidney cancer that has spread.

6. keytrudalenvimahcp.com keytrudalenvimahcp.com/advanced-renal-cell-carcinoma/

Advanced Renal Cell Carcinoma: Efficacy and Safety Results Health care professionals can review efficacy data and safety results for a first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

7. cancernetwork.com cancernetwork.com/view/perioperative-lenvatinib-combo-shows-activity-in-advanced-clear-cell-rcc

Perioperative Lenvatinib Combo Shows Activity in ... Treatment elicited a median primary renal tumor size reduction of 21.8% (range, 3.4%-37.0%). There were no instances of disease progression ...