Pembrolizumab for Kidney Cancer

(MRD GATE RCC Trial)

Overseen By Arnab Basu, MD,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

Trial Summary

What is the purpose of this trial?

The goal of this Clinical Study is to understand the outcomes by informing therapy choice for adjuvant treatment in clear cell renal cell carcinoma by using molecular residual disease. The main question\[s\] it aims to answer are: * what is the progression free survival of a cohort of high risk resected RCC patients when treated based on MRD * what is the overall survival of high risk resected RCC patients when treated based on MRD Participants will forgo adjuvant therapy with pembrolizumab if they have no detectable molecular residual disease. Participants will continue on with standard of care pembrolizumab if they do appear to have molecular residual disease.

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.

What data supports the effectiveness of the drug pembrolizumab for kidney cancer?

Research shows that pembrolizumab helps improve disease-free survival (the time patients live without the cancer coming back) in people with kidney cancer after surgery. In a study, patients who took pembrolizumab had better outcomes compared to those who took a placebo (a substance with no active drug). ^{1 2 3 4 5}

Is pembrolizumab generally safe for humans?

Pembrolizumab, also known as Keytruda, has been associated with some side effects, including pneumonitis (lung inflammation) in 1%-5% of patients and rare cases of type 1 diabetes. Common side effects include fatigue, cough, nausea, and rash, but it has been generally well-tolerated in clinical trials. ^{1 6 7 8 9}

How is the drug pembrolizumab unique for treating kidney cancer?

Pembrolizumab is unique because it is an immune checkpoint inhibitor that targets the PD-1 pathway, helping the immune system recognize and attack cancer cells. This mechanism is different from traditional chemotherapy, which directly kills cancer cells, and it has shown effectiveness in various cancers, including lung and melanoma, suggesting potential benefits for kidney cancer. ^{1 10 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 (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]

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, 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]

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, 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, 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]

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 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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Adjuvant therapy for patients with renal cell carcinoma following surgery: a focus on pembrolizumab. [2022]

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

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

4. Germany pubmed.ncbi.nlm.nih.gov

How to optimize the use of adjuvant pembrolizumab in renal cell carcinoma: which patients benefit the most? [2023]

5. England 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. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

9. United States 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. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

12. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. [2019]

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

Tolerability and treatment outcome of pembrolizumab in patients with advanced urothelial carcinoma and severe renal dysfunction. [2022]