Pembrolizumab + Lenvatinib for Kidney Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Vivek K. Narayan

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Metastatic disease, Cardiovascular disease, Autoimmune disease, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment alone or in combination with another treatment in kidney cancer patients to see if these treatments improve the body's defense system against cancer around the time of surgery. The treatments help the body attack cancer and stop its growth. These treatments have shown promising results in various cancers, especially kidney cancer.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have changes in antihypertensive medications within 1 week prior to randomization, and those on chronic systemic steroid therapy above a certain dose are excluded. 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 kidney cancer?

Research shows that the combination of pembrolizumab and lenvatinib is effective in treating advanced renal cell carcinoma, with studies indicating improved survival rates compared to other treatments like sunitinib. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Lenvatinib safe for humans?

The combination of Pembrolizumab and Lenvatinib has been studied for safety in patients with advanced kidney cancer and other solid tumors. Common side effects were identified, and strategies for managing these side effects were reviewed, indicating that while there are adverse reactions, they can be managed. ^{2 3 5 6 7}

How is the drug pembrolizumab + lenvatinib unique for kidney cancer?

Pembrolizumab + lenvatinib is unique for kidney cancer because it combines an immune checkpoint inhibitor (pembrolizumab) with a multikinase inhibitor (lenvatinib), offering a novel approach that targets both the immune system and cancer cell growth pathways, which has shown improved outcomes compared to some existing treatments. ^{1 2 3 4 6}

Research Team

Vivek K. Narayan

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

Adults with confirmed renal cell carcinoma, eligible for kidney cancer surgery, can join this trial. They must have good organ function and controlled blood pressure, not be pregnant or breastfeeding, use effective contraception if applicable, and have no recent major surgeries or active infections. Those with certain heart conditions, other cancers within 3 years, severe drug allergies or immune diseases are excluded.

Inclusion Criteria

My organs are working well.

My blood pressure is under control, with or without medication.

The participant (or legally acceptable representative if applicable) provides written informed consent for the trial

Exclusion Criteria

I have a history of Hepatitis B or an active Hepatitis C infection.

I have been treated with cancer-fighting drugs before.

I have an immune system disorder or I am on long-term steroids.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Systemic Therapy

Participants receive pembrolizumab with or without lenvatinib as neoadjuvant therapy before surgical nephrectomy

4 weeks

1 visit every 3 weeks (in-person)

Surgical Resection

Participants undergo surgical nephrectomy to remove kidney cancer

1 week

1 visit (in-person)

Adjuvant Systemic Pembrolizumab Therapy

Participants receive pembrolizumab as adjuvant therapy post-surgery

18-24 months

1 visit every 3 weeks (in-person)

Post-Treatment Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

Treatment Details

Interventions

• Lenvatinib (Tyrosine Kinase Inhibitor)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview The study tests pembrolizumab (infusion) alone or combined with lenvatinib (tablet) on the body's immune response to kidney cancer before and after surgical removal of the tumor. The goal is to see how these drugs affect the disease when used as a pre-surgery treatment.

Participant Groups

Group I: B: Pembrolizumab Experimental Treatment 1 Intervention

Subject will receive Pembrolizumab 200 mg or 400 mg will be administered as a 30-minute IV infusion every 3 weeks.

Group II: A: Pembrolizumab + Lenvatinib Experimental Treatment 2 Interventions

Subjects will receive Pembrolizumab + Lenvatinib. Pembrolizumab 200 mg or 400 mg will be administered as a 30-minute IV infusion every 3 weeks. Lenvatinib 20 mg daily will be self-administered PO by subject for 28 consecutive days, beginning Day -7.

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Dr. Robert H. Vonderheide

Abramson Cancer Center of the University of Pennsylvania

Chief Executive Officer since 2017

DPhil in Immunology from Oxford University, MD from Harvard Medical School

Dr. Lawrence N. Shulman

Abramson Cancer Center of the University of Pennsylvania

Chief Medical Officer since 2017

MD from Harvard Medical School

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Dr. Robert H. Vonderheide

Abramson Cancer Center at Penn Medicine

Chief Executive Officer since 2017

MD from Harvard Medical School

Dr. Bonnie Ky

Abramson Cancer Center at Penn Medicine

Chief Medical Officer

MD, MSCE from University of Pennsylvania

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

Findings from Research

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 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]

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 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 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]

References

1. England 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. [2022]

2. England 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. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. [2022]

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

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. [2022]

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

Lenvatinib plus pembrolizumab versus sunitinib for advanced renal cell carcinoma: Japanese patients from the CLEAR study. [2023]

6. England 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. [2023]

7. England 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. [2023]