Pembrolizumab for Kidney Cancer

Not currently recruiting at 303 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Brain metastases, Active infection, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if pembrolizumab, administered by IV infusion, can prevent kidney cancer from returning after surgery. It targets individuals who have had their kidney tumor removed and face a higher risk of recurrence. Participants will receive either pembrolizumab or a placebo every three weeks for up to a year. The trial seeks individuals who have undergone kidney cancer surgery, are currently cancer-free, and have not received prior treatments for advanced kidney cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these medications before starting the trial.

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

Research has shown that pembrolizumab is generally well-tolerated by people with kidney cancer. In one study, patients who took pembrolizumab lived longer without the disease returning compared to those who took a placebo. This finding suggests that the treatment is effective and safe for use after kidney surgery.

Some patients who received pembrolizumab reported side effects, but these were often manageable. Common issues included fatigue, rash, and mild nausea. Serious side effects were less common and typically treated with medical care. The FDA has already approved pembrolizumab for other conditions, which supports its safety for human use.

Overall, pembrolizumab has demonstrated a good safety record, making it a promising option for those considering this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it leverages the power of the immune system to fight kidney cancer. Unlike standard treatments such as tyrosine kinase inhibitors, which target cancer cell growth, pembrolizumab is an immune checkpoint inhibitor that blocks the PD-1 protein on immune cells, enhancing their ability to attack cancer cells. This novel mechanism of action has researchers excited as it represents a shift from directly targeting the cancer cells to empowering the body's natural defenses, potentially offering a more effective and durable response.

What evidence suggests that pembrolizumab could be an effective treatment for kidney cancer?

In this trial, participants will receive either pembrolizumab or a placebo. Research has shown that pembrolizumab can help kidney cancer patients remain cancer-free for longer. In one study, patients who took pembrolizumab after surgery had better outcomes than those who took a placebo (a harmless pill with no active drug). Specifically, the chance of cancer returning was lower for those on pembrolizumab. Another study found that 91.2% of patients on pembrolizumab were still alive, compared to 86% of those on a placebo. These findings suggest that pembrolizumab may be more effective in reducing the risk of cancer recurrence. ^{3 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?

Adults who've had kidney cancer surgery with intermediate to high risk of recurrence, or no evidence of disease after metastasis removal. They must have good organ function, agree to contraception for 120 days post-treatment, and not have received prior advanced RCC therapy. Exclusions include recent other cancer treatments, major surgeries (other than nephrectomy/metastasectomy), dialysis history, active infections like HIV/hepatitis B/C, pregnancy/breastfeeding intentions during the study period.

Inclusion Criteria

My organs are functioning well.

I had surgery to remove a kidney or cancer spread at least 28 days ago but no more than 12 weeks ago.

My kidney cancer diagnosis includes clear cell characteristics.

Exclusion Criteria

I have had cancer before, but it was treated and is not currently active, except for certain skin cancers or early-stage cancers.

I have blood clots in my veins after kidney surgery.

I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab or placebo via IV infusion every 3 weeks for up to 17 cycles (approximately 1 year)

12 months

17 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 72 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Placebo

Trial Overview The trial tests pembrolizumab's effectiveness in preventing kidney cancer from returning after surgery compared to a placebo. Participants are randomly assigned to receive either pembrolizumab or a placebo and monitored for disease-free survival as the main outcome.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year).

Group II: Placebo Placebo Group 1 Intervention

Participants receive placebo (saline solution) via IV infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year).

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

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

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor for non-small cell lung carcinoma, has been linked to adverse renal outcomes, including acute kidney injury.

In a reported case, a patient developed acute tubulointerstitial nephritis after starting pembrolizumab, and while renal function improved with long-term corticosteroid treatment after discontinuation of the drug, it only improved partially.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab. Basnet, S., Dhital, R., Tharu, B.[2020]

Pembrolizumab can be safely administered to patients with severe renal dysfunction (creatinine clearance <30 ml/min), showing similar safety profiles and treatment-related adverse events compared to those with normal renal function.

Patients with severe renal dysfunction had comparable overall survival rates and response rates to pembrolizumab as those with better kidney function, indicating that this treatment remains effective even in this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and treatment outcome of pembrolizumab in patients with advanced urothelial carcinoma and severe renal dysfunction. Kita, Y., Ito, K., Kanda, S., et al.[2022]

This study presents the first known case of a patient with metastatic melanoma who was successfully treated with pembrolizumab while undergoing hemodialysis, highlighting its potential efficacy in patients with end-stage renal disease.

Pembrolizumab, an FDA-approved monoclonal antibody for metastatic melanoma and non-small cell lung cancer, shows promise for use in patients with renal complications, although specific dosing guidelines for such patients are still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. Chang, R., Shirai, K.[2019]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Adjuvant pembrolizumab significantly improves disease-free survival in patients with high-risk renal cell carcinoma (RCC) after surgery, as shown in the KEYNOTE 564 trial.

Pembrolizumab is an effective and well-tolerated treatment option for patients with surgically resected RCC, paving the way for future research on patient selection and biomarkers for therapy response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant therapy for patients with renal cell carcinoma following surgery: a focus on pembrolizumab. Serzan, M., Atkins, MB.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In the off-trial setting, patients with high-risk renal cell carcinoma (RCC) showed worse tumor characteristics and disease-free survival (DFS) compared to those in the KEYNOTE-564 trial, indicating a need for careful patient selection for adjuvant pembrolizumab.

Patients with lymph node involvement (LNI) or necrosis were identified as the highest risk group for early recurrence, suggesting they are the most suitable candidates for receiving adjuvant pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to optimize the use of adjuvant pembrolizumab in renal cell carcinoma: which patients benefit the most? Fallara, G., Larcher, A., Rosiello, G., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

The combination of axitinib and pembrolizumab shows a high response rate of 73% in patients with previously untreated advanced renal cell carcinoma, indicating strong efficacy for this treatment regimen.

This finding suggests that the dual approach of targeting both tumor growth and immune response may be effective in managing advanced kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

In the KEYNOTE-564 study involving 994 participants, adjuvant pembrolizumab significantly improved disease-free survival in patients with clear cell renal cell carcinoma at increased risk of recurrence, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of recurrence compared to placebo.

The safety profile of pembrolizumab was acceptable, with serious adverse events occurring in 12% of participants receiving the treatment, but no deaths were attributed to the drug, supporting its use as a standard care option post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Powles, T., Tomczak, P., Park, SH., et al.[2023]

Citations

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

Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell ... Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer.

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

Open-Label, Single-Arm Phase II Study of Pembrolizumab ... Pembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types.

3. 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 ...

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. 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 ...

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. 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).