Pembrolizumab for Kidney Cancer
(MRD GATE RCC Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 3 Jurisdictions
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).
12345Is 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.
16789How 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.
110111213Eligibility 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
+11 more
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.
+14 more
Trial 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
Participant Groups
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.
2Treatment groups
Active Control
Group I: Arm 2 MRD positive patientsActive Control1 Intervention
Patients are treated with Pembrolizumab 400 mg IV q 6 weeks for a total of 1 year
Group II: Arm 1: MRD negative patientsActive Control1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Alabama at BirminghamBirmingham, AL
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Who Is Running the Clinical Trial?
University of Alabama at BirminghamLead Sponsor
References
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Adjuvant therapy for patients with renal cell carcinoma following surgery: a focus on pembrolizumab. [2022]Many patients with renal cell carcinoma (RCC) who undergo surgery with curative intent have a high risk of disease recurrence and until recently no palatable adjuvant systemic therapy options. Blocking the programmed death ligand (PD-1) immune checkpoint pathway with pembrolizumab has robust clinical efficacy in patients with metastatic RCC. Results from the KEYNOTE 564 trial demonstrate that adjuvant pembrolizumab significantly improves disease- free survival after nephrectomy or metastasectomy.
Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]Axitinib plus pembrolizumab has a 73% response rate in previously untreated advanced renal cell carcinoma.
How to optimize the use of adjuvant pembrolizumab in renal cell carcinoma: which patients benefit the most? [2023]The KEYNOTE-564 trial showed improved disease-free survival (DFS) for patients with high-risk renal cell carcinoma (RCC) receiving adjuvant pembrolizumab as compared to placebo. However, if systematically administered to all high-risk patients, it might lead to the overtreatment in a non-negligible proportion of patient. Therefore, we aimed to determine the optimal candidate for adjuvant pembrolizumab.
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]The first interim analysis of the KEYNOTE-564 study showed improved disease-free survival with adjuvant pembrolizumab compared with placebo after surgery in patients with clear cell renal cell carcinoma at an increased risk of recurrence. The analysis reported here, with an additional 6 months of follow-up, was designed to assess longer-term efficacy and safety of pembrolizumab versus placebo, as well as additional secondary and exploratory endpoints.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint, which may be engaged by cells in the tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda®, MK-3475) is a potent and highly selective humanized mAb of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances the functional activity of T cells to facilitate tumor regression and ultimately immune rejection. Pembrolizumab binds to human and cynomolgus monkey PD-1 with picomolar affinity and blocks the binding of human and cynomolgus monkey PD-1 to PD-L1 and PD-L2 with comparable potency. Pembrolizumab binds both the C'D and FG loops of PD-1. Pembrolizumab overcomes human and cynomolgus monkey PD-L1-mediated immune suppression in T-cell cultures by enhancing IL2 production following staphylococcal enterotoxin B stimulation of healthy donor and cancer patient cells, and IFNγ production in human primary tumor histoculture. Ex vivo and in vitro studies with human and primate T cells show that pembrolizumab enhances antigen-specific T-cell IFNγ and IL2 production. Pembrolizumab does not mediate FcR or complement-driven effector function against PD-1-expressing cells. Pembrolizumab displays dose-dependent clearance and half-life in cynomolgus monkey pharmacokinetic and toxicokinetic studies typical for human IgG4 antibodies. In nonhuman primate toxicology studies, no findings of toxicologic significance were observed. The preclinical data for pembrolizumab are consistent with the clinical anticancer activity and safety that has been demonstrated in human clinical trials.
Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab. [2020]Pembrolizumab is a novel immune checkpoint inhibitor approved for use in non-small cell lung carcinoma. There have been a few cases that have associated adverse renal outcomes with pembrolizumab. We present a case of acute kidney injury in a patient on pembrolizumab who was noted to have acute tubulointerstitial nephritis on renal biopsy. Pembrolizumab was discontinued and the patient was started on long-term corticosteroids with a taper. Her renal function improved partially with treatment.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. [2019]Patients with end-stage renal disease present with a distinct challenge in oncology. Many anticancer drugs and their metabolites are excreted by the kidney, but data to guide dose and schedule adjustments in renal dialysis are scant. Pembrolizumab is an anti-programmed cell death protein 1 monoclonal antibody proven to be effective in patients with metastatic melanoma. It has demonstrated promising results and was granted US Food and Drug Administration (FDA) approval in September, 2014 for metastatic melanoma. It was additionally approved for patients with metastatic non-small cell lung cancer by the FDA in October, 2015. We present the first case, to the best of our knowledge, of a patient with metastatic melanoma successfully treated with pembrolizumab while on haemodialysis.
Tolerability and treatment outcome of pembrolizumab in patients with advanced urothelial carcinoma and severe renal dysfunction. [2022]Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment of advanced urothelial carcinoma. However, the tolerability and outcomes of pembrolizumab in patients with severe renal dysfunction [creatinine clearance (CrCl)