Pembrolizumab + Lenvatinib for Kidney Cancer

(KEYNOTE-B61 Trial)

Not currently recruiting at 72 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Cardiovascular disease, 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: 18

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the potential benefits of combining two treatments, pembrolizumab (an immunotherapy drug) and lenvatinib (a targeted therapy), for individuals with untreated advanced kidney cancer. The focus is on non-clear cell renal cell carcinoma, a type that can be challenging to treat. Participants with advanced kidney cancer who haven't received prior treatment for this stage might be suitable candidates. The goal is to determine if this combination can help manage the disease. As a Phase 2 trial, the research measures 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, it mentions that you must not have received prior systemic therapy for advanced kidney cancer and should have controlled blood pressure, which might imply some restrictions. 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?

A previous study found that about 25% of patients experienced serious side effects when using the combination of pembrolizumab and lenvatinib. These side effects were severe enough that 33.3% of patients needed to reduce their lenvatinib dose. However, this treatment has helped patients live longer compared to another drug, sunitinib.

The FDA has also approved pembrolizumab and lenvatinib for treating other types of kidney cancer, indicating they are generally safe when used under a doctor's care. While side effects can occur, healthcare providers closely monitor patients to manage any issues that arise. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Pembrolizumab and Lenvatinib for kidney cancer because they bring a novel approach to treatment. Unlike traditional treatments like surgery or standard chemotherapy, Pembrolizumab is an immunotherapy that enhances the body's immune system to fight cancer cells. Lenvatinib, on the other hand, is a targeted therapy that inhibits proteins responsible for tumor growth. This combination offers a two-pronged attack: boosting immune response while directly targeting cancer cell pathways. This dual action has the potential to improve outcomes for patients with kidney cancer compared to existing treatment options.

What evidence suggests that the combination of pembrolizumab and lenvatinib might be an effective treatment for kidney cancer?

Research has shown that the combination of pembrolizumab and lenvatinib, which participants in this trial will receive, holds promise for treating advanced kidney cancer. Studies have found that 66% of patients experience a significant reduction in tumor size. The median time before the cancer worsens is 20.1 months. Long-term studies also indicate high survival rates, with 80.4% of patients alive at 24 months and 66.4% at 36 months. These results suggest that this treatment combination can be effective for those with advanced kidney cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced/metastatic non-clear cell renal cell carcinoma who haven't had systemic therapy for it. They must have a confirmed diagnosis, measurable disease, good performance status (KPS ≥70%), and adequate organ function. Women of childbearing potential must agree to contraception during treatment and afterwards (120 days post pembrolizumab or 30 days post lenvatinib).

Inclusion Criteria

My organs are functioning well.

My cancer can be measured and has grown in areas previously treated with radiation.

My cancer is at stage IV.

Exclusion Criteria

My heart's pumping ability is below the normal range.

I have coughed up bright red blood recently.

My kidney cancer is of a type called collecting duct.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pembrolizumab 400 mg every 6 weeks and Lenvatinib 20 mg daily until progressive disease or discontinuation

Up to 3 years

18 visits (in-person) for Pembrolizumab infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The study tests the combination of two drugs, Pembrolizumab and Lenvatinib, in patients with untreated kidney cancer that has spread. It's an open-label study where all participants receive the same treatment to quickly assess its benefits.

How Is the Trial Designed?

Group I: Pembrolizumab + Lenvatinib Experimental Treatment 2 Interventions

Pembrolizumab 400 mg, every 6 weeks (Q6W) intravenous (IV) up to 18 infusions or up to progressive disease or discontinuation PLUS Lenvatinib 20 mg, daily (QD), oral, until progressive disease or discontinuation.

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?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead 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

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Published Research Related to This Trial

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 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]

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]

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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40343572/

real-world evidences from the international ARON- 1 study Conclusions: Pembrolizumab plus lenvatinib is an effective and tolerable treatment for mRCC also in the real-world setting. Keywords: ARON- 1; ...

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

Effectiveness, toxicity and treatment adjustments of ... In our real-world population, the effectiveness of lenvatinib plus pembrolizumab could clearly be confirmed with an ORR of 66% and an mPFS of 20.1 months for ...

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® ... The 24- and 36-month estimated OS rates were 80.4% and 66.4% for KEYTRUDA plus LENVIMA versus 69.6% and 60.2% for sunitinib, respectively. Results from the ...

4. 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 ... Improved efficacy with lenvatinib + pembrolizumab continued to be observed after ~4 years of follow-up (data cutoff: 31 July 2022):. As such, at ...

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

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

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11964907/

and poor-risk metastatic renal cell carcinoma - PMC Grade ≥ 3 adverse events occurred in 25% of patients, with 33.3% requiring lenvatinib dose reductions. Lenvatinib plus pembrolizumab ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2035716

Lenvatinib plus Pembrolizumab or Everolimus for ... Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05733715

Neoadjuvant Pembrolizumab and Lenvatinib for Renal Cell ... This trial will generate preliminary data on immune pharmacodynamic outcomes and tumor response for neoadjuvant pembrolizumab +/- lenvatinib and is not powered ...