Pembrolizumab for Kidney Cancer

(MRD GATE RCC Trial)

Overseen By Margaret A Thomas, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must be taking: Pembrolizumab

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Autoimmune disease, Dialysis, others

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

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

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

Compensation: Varies

Number of Visits: 9

Duration: 52 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab to evaluate its effectiveness for individuals with high-risk kidney cancer (renal cell carcinoma) after surgery. Researchers aim to determine if treatment based on molecular residual disease (MRD) can extend the time patients live without cancer recurrence and improve overall survival. Participants without detectable MRD will skip additional treatment, while those with MRD will continue with pembrolizumab. Eligible participants should have recently undergone kidney cancer surgery, be tumor-free, and not have received prior systemic therapy for advanced kidney cancer, except for limited pembrolizumab treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop as these are exclusion criteria.

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

Research has shown that pembrolizumab is generally well-tolerated. Studies have found that it can extend the lives of patients with kidney cancer. Specifically, one study demonstrated that pembrolizumab reduced the risk of cancer recurrence after surgery.

Patients in these studies experienced side effects, but most were manageable. Common side effects included fatigue and skin reactions, while serious side effects were less common.

Since pembrolizumab is already approved for other cancer treatments, extensive safety information is available. This provides doctors with a solid understanding of its mechanism in the body and the expected side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for kidney cancer?

Pembrolizumab is unique because it harnesses the power of the immune system to target kidney cancer cells. Unlike traditional treatments like targeted therapies or chemotherapy, pembrolizumab is an immune checkpoint inhibitor that blocks PD-1, a protein on cells that helps keep the immune system from attacking cancer. By blocking PD-1, pembrolizumab boosts the immune response against cancer cells, potentially leading to more effective and long-lasting results. Researchers are excited because this approach offers a novel way to treat kidney cancer, particularly in patients who might not respond well to existing therapies.

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

Research shows that pembrolizumab can help treat high-risk kidney cancer after surgery. In this trial, participants in Arm 2, who are MRD positive, will receive pembrolizumab. Studies found that 24 months after treatment, 77.3% of patients who received pembrolizumab were free of the disease, compared to those who received a placebo. Another study showed that after 48 months, 91.2% of patients taking pembrolizumab were still alive, compared to 86.0% of those on a placebo. Pembrolizumab helps the immune system find and destroy cancer cells, which can lower the chance of the cancer returning. These results suggest that pembrolizumab is a promising treatment option for kidney cancer after surgery. ^{2 3 5 6 7}

Who Is on the Research Team?

Charles A Peyton, MD

Principal Investigator

The University of Alabama at Birmingham

Are You a Good Fit for This Trial?

Adults over 18 who've had kidney cancer surgery within the last 12 weeks, are tumor-free, and have certain high-risk factors. They must not be pregnant or breastfeeding, agree to use contraception, and have no history of severe immune conditions or recent live vaccines. Participants with detectable molecular residual disease will receive pembrolizumab; those without won't.

Inclusion Criteria

My kidney cancer is considered high risk based on its size, spread, and grade.

I have advanced kidney cancer and have only started immunotherapy with pembrolizumab recently.

The participant provides written informed consent for the trial

Exclusion Criteria

You have been diagnosed with HIV.

I have another cancer that is growing or was treated within the last 3 years.

I am currently on or have a history of dialysis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

MRD positive patients receive Pembrolizumab 400 mg IV every 6 weeks for a total of 1 year

52 weeks

9 visits (in-person)

Observation

MRD negative patients undergo observation without adjuvant therapy

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests if using molecular residual disease (MRD) to guide the use of pembrolizumab improves progression-free and overall survival in high-risk kidney cancer patients after surgery. Those with MRD get pembrolizumab; those without do not.

How Is the Trial Designed?

Group I: Arm 2 MRD positive patients Active Control 1 Intervention

Patients are treated with Pembrolizumab 400 mg IV q 6 weeks for a total of 1 year

Group II: Arm 1: MRD negative patients Active Control 1 Intervention

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

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]

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, 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 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, 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]

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]

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 (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]

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]

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]

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]

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]

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. 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. 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 ...

5. keytruda.com keytruda.com/kidney-cancer/adjuvant-clinical-trial-results/

results from a clinical trial. In a clinical trial of patients who had surgery to remove their kidney cancer, 496 patients who received 200 mg of KEYTRUDA every 3 weeks were compared to 498 ...

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. 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).