Lenvatinib + Pembrolizumab for Kidney Cancer

No longer recruiting at 4 trial locations

Overseen By Joel Picus

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Biologic response modifiers

Disqualifiers: Clear cell RCC, Brain metastasis, Heart failure, 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: 3

Duration: Approximately 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the effectiveness and safety of combining two drugs, lenvatinib (a targeted therapy) and pembrolizumab (an immunotherapy), for treating a specific type of advanced kidney cancer. It focuses on individuals with advanced non-clear cell renal carcinoma who have not undergone chemotherapy for their advanced disease. Ideal candidates for this trial are those with aggressive forms of kidney cancer that cannot be surgically removed and who have not previously received systemic treatment for advanced disease. As a Phase 2 trial, the research focuses on assessing 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 does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial team to ensure they don't interfere with the study treatments.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of lenvatinib and pembrolizumab has yielded promising results, though challenges remain. In these studies, 25% of patients experienced serious side effects, classified as grade 3 or higher adverse events. These significant side effects could be managed with medical care. Additionally, about one-third of the patients required lenvatinib dose reductions to better manage these side effects.

Notably, a small number of patients experienced kidney problems, specifically kidney failure or damage, in 2-3% of cases. Despite these risks, the combination has improved survival rates for patients with advanced kidney cancer, suggesting that while side effects exist, potential treatment benefits may outweigh them. ^{1 2 3 4 5}

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

Researchers are excited about the combination of Lenvatinib and Pembrolizumab for kidney cancer because it offers a fresh approach to treatment. Unlike traditional therapies that often rely on surgery or chemotherapy, this duo combines a targeted therapy (Lenvatinib) with an immune checkpoint inhibitor (Pembrolizumab). Lenvatinib works by blocking certain proteins that promote tumor growth, while Pembrolizumab enhances the immune system's ability to attack cancer cells. This combination could potentially improve outcomes by tackling the cancer from two different angles, offering hope for more effective management of kidney cancer.

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

Research has shown that using lenvatinib and pembrolizumab together appears promising for treating kidney cancer. In one study, 66% of patients responded positively, with their tumors either shrinking or ceasing to grow. Another study found that patients lived for an average of 20.1 months without their cancer worsening. Additionally, evidence indicates that individuals taking this combination lived longer than those on another common treatment, sunitinib. This trial will specifically evaluate the combination of lenvatinib and pembrolizumab, suggesting it could be a strong option for treating advanced kidney cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Joel Picus

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults with advanced or metastatic non-clear cell renal carcinoma who haven't had chemotherapy for advanced disease. They must have specific subtypes of kidney cancer, normal blood pressure, adequate organ function, and no major surgery within the last month. Women must not be pregnant and agree to contraception; men also need to follow certain contraceptive guidelines.

Inclusion Criteria

Ability to understand and willingness to sign an IRB approved written informed consent document

I am using birth control as a man with a partner who can have children.

I can provide a recent tumor sample for testing.

Exclusion Criteria

I have or had lung inflammation needing steroids, not caused by an infection.

I have had serious heart issues, like a heart attack or unstable angina, in the last 6 months.

I have had an organ or stem cell transplant from a donor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib 20 mg/day orally and pembrolizumab 200 mg every 3 weeks for up to 35 cycles or approximately 2 years

Approximately 2 years

Pembrolizumab administered every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up lasting up to 120 days after the last day of study treatment

Approximately 4 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Median length 602 days

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab
• Research blood collection

Trial Overview The trial is testing a combination of two drugs: Lenvatinib (20 mg/day) and Pembrolizumab (200mg every three weeks), along with research blood collection in patients with certain types of kidney cancer that has spread and cannot be surgically removed.

How Is the Trial Designed?

Group I: Lenvatinib + Pembrolizumab Experimental Treatment 3 Interventions

* Lenvatinib 20 mg/day will be administered orally on a daily basis and pembrolizumab 200 mg will be infused once every 3 weeks. * Subjects may be treated with pembrolizumab for a maximum of 35 cycles or approximately 2 years, but treatment with lenvatinib can continue beyond 2 years if the subject does not meet other treatment discontinuation criteria.

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?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

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

Citations

1. 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 ...

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 ... In patients treated with lenvatinib + pembrolizumab, IMDC scores generally improved or remained constant over 6 months, both in patients with ...

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

and poor-risk metastatic renal cell carcinoma - PMC The median duration of lenvatinib plus pembrolizumab therapy was 15.7 months. The ORR was 48.33%, with 5.0% achieving complete responses and ...

4. 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.

5. 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 ...

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

Advanced Renal Cell Carcinoma (RCC) Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study. In RCC, renal ...