Pembrolizumab + Lenvatinib for Kidney Cancer

Overseen By Matt Doyle

Age: 18+

Sex: Any

Trial Phase: Phase < 1

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 All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two investigational drugs, pembrolizumab (an immunotherapy drug) and lenvatinib (a targeted therapy drug), can help the immune system combat kidney cancer. Researchers aim to assess the effects of these drugs when administered before and after surgery to remove kidney cancer. Participants will receive either pembrolizumab alone or a combination of pembrolizumab and lenvatinib. The trial seeks individuals with kidney cancer who plan to undergo surgery and have a confirmed diagnosis. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants a chance to contribute to groundbreaking medical knowledge.

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.

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

Research has shown that the drugs pembrolizumab and lenvatinib, both separately and together, have been studied for safety in treating different types of kidney cancer. Studies found that using pembrolizumab with lenvatinib is effective for patients with advanced kidney cancer, achieving a 50.6% response rate and an 82.3% disease control rate. This combination is already used as a first treatment option for some kidney cancer patients.

Pembrolizumab alone has also been tested for safety in kidney cancer and has been shown to help patients live longer after kidney cancer surgery. These treatments have been studied enough to demonstrate they are generally well-tolerated. However, like any medication, they can have side effects. Always consult your doctor about what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Pembrolizumab and Lenvatinib offer a fresh approach to tackling kidney cancer. Unlike standard treatments, which often involve targeted therapies or immunotherapies separately, this combination leverages both an immune checkpoint inhibitor (Pembrolizumab) and a tyrosine kinase inhibitor (Lenvatinib). Pembrolizumab works by blocking a protein called PD-1, boosting the immune system to attack cancer cells more effectively. Lenvatinib, on the other hand, inhibits the growth of blood vessels that supply the tumor, starving it of nutrients. This dual mechanism has the potential to enhance the overall effectiveness against kidney cancer compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

Research has shown that using pembrolizumab and lenvatinib together, which participants in this trial may receive, holds promise for treating advanced kidney cancer. In studies, this combination achieved a 51% overall response rate, with more than half of the patients experiencing tumor shrinkage or disappearance. This treatment also improved survival rates, proving more effective than the standard treatment with sunitinib.

Meanwhile, pembrolizumab alone, another treatment option in this trial, has helped patients remain cancer-free for longer after surgery. Specifically, after 48 months, 91.2% of patients taking pembrolizumab were still alive, compared to 86% of those taking a placebo. These findings suggest that both treatments could be effective for kidney cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Vivek K. Narayan

Principal Investigator

Abramson Cancer Center at Penn Medicine

Are You a Good Fit for This Trial?

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 haven't had serious heart problems in the last year.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

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.

How Is the Trial Designed?

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+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

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 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]

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 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 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2106391

Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell ... Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.LBA359

Overall survival results from the phase 3 KEYNOTE-564 ... Adjuvant pembrolizumab improved disease-free survival (DFS) compared with placebo following nephrectomy in participants (pts) with ccRCC at an increased risk ...

3. keytrudahcp.com keytrudahcp.com/efficacy/adjuvant-renal-cell-carcinoma/

KEYNOTE-564 - Clinical Trial Results & Study Design | HCP Health care professionals may find clinical trial results from KEYNOTE-564 for the adjuvant treatment of certain patients with renal cell carcinoma (RCC).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03142334

Safety and Efficacy Study of Pembrolizumab (MK-3475) as ... The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in the adjuvant treatment of adult participants who have ...

5. merck.com merck.com/news/mercks-keytruda-pembrolizumab-reduced-the-risk-of-death-by-38-versus-placebo-as-adjuvant-therapy-for-patients-with-renal-cell-carcinoma-rcc-at-an-increased-risk-of-recurrence-follow/

Merck's KEYTRUDA® (pembrolizumab) Reduced the Risk ... At 48 months, the estimated OS rate was 91.2% for patients who received KEYTRUDA compared to 86.0% for patients who received placebo. The OS benefit for ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT3142334

Safety and Efficacy Study of Pembrolizumab (MK-3475) as ... The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in the adjuvant treatment of adult participants who have ...

7. merck.com merck.com/news/merck-announces-keytruda-pembrolizumab-plus-welireg-belzutifan-met-primary-endpoint-of-disease-free-survival-dfs-in-certain-patients-with-clear-cell-renal-cell-carcinoma-rcc-follow/

Merck Announces KEYTRUDA® (pembrolizumab) Plus ... First combination regimen to demonstrate improvement in DFS compared to KEYTRUDA monotherapy for these patients in the adjuvant setting.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8078336/

Open-Label, Single-Arm Phase II Study of Pembrolizumab ... The phase II KEYNOTE-427 study evaluated efficacy and safety of single-agent pembrolizumab in treatment-naive patients with advanced clear cell renal cell ...

9. 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).