V940 + Pembrolizumab for Kidney Cancer
(INTerpath-004 Trial)
Recruiting in Palo Alto (17 mi)
+65 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Merck Sharp & Dohme LLC
Must be taking: Pembrolizumab
Must not be taking: Steroids, Cancer vaccines
Disqualifiers: Immunodeficiency, Active malignancy, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The primary objective of the study is to compare V940 plus pembrolizumab to placebo plus pembrolizumab in participants with renal cell carcinoma (RCC) with respect to disease-free survival (DFS) as assessed by the investigator. The primary hypothesis is that V940 plus pembrolizumab is superior to placebo plus pembrolizumab with respect to DFS.
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 systemic anticancer therapy, steroids, or have received a live vaccine recently, you may need to stop those before joining the trial.
What data supports the effectiveness of the drug Pembrolizumab for kidney cancer?
Research shows that pembrolizumab, when used as an adjuvant therapy (additional treatment given after the primary treatment), significantly improves disease-free survival in patients with renal cell carcinoma after surgery. Additionally, a combination of axitinib and pembrolizumab has shown a 73% response rate in advanced renal cell carcinoma.
12345Is the combination of V940 and Pembrolizumab safe for humans?
Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, and nausea. Some serious side effects include pneumonitis (lung inflammation), colitis (colon inflammation), and thyroid disorders. There have also been rare cases of kidney issues, so it's important to discuss potential risks with your doctor.
14678How does the drug V940 + Pembrolizumab differ from other kidney cancer treatments?
Pembrolizumab is a unique drug because it is an immune checkpoint inhibitor that helps the body's immune system attack cancer cells by blocking the PD-1 pathway, which is different from traditional chemotherapy that directly kills cancer cells. This combination with V940 may offer a novel approach for kidney cancer by potentially enhancing the immune response against the tumor.
13489Eligibility Criteria
This trial is for adults with a specific kidney cancer (clear cell or papillary renal cell carcinoma). They should be at intermediate-high risk, have had surgery to remove the tumor and any isolated metastases within the last 12 weeks, and be in good physical condition (ECOG status of 0 or 1).Inclusion Criteria
My kidney cancer is confirmed to be either clear cell or papillary type.
My kidney cancer is at an intermediate to high risk level or I have no signs of disease after metastasis.
I had surgery to remove my primary cancer and any solid metastatic tumors.
+2 more
Exclusion Criteria
I haven't had cancer treatment or experimental drugs in the last 4 weeks.
I haven't had radiotherapy or needed steroids for side effects in the last 2 weeks.
I have not received a live vaccine in the last 30 days.
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive V940 or placebo plus Pembrolizumab for up to 54 weeks
54 weeks
9 visits (in-person) every 6 weeks
Follow-up
Participants are monitored for disease-free survival and overall survival
43 months
Long-term follow-up
Participants are monitored for overall survival and distant metastasis-free survival
96 months
Participant Groups
The study aims to see if adding V940 to pembrolizumab improves disease-free survival compared to using pembrolizumab with a placebo. Participants will randomly receive either the combination of V940 and pembrolizumab or a placebo plus pembrolizumab.
2Treatment groups
Experimental Treatment
Active Control
Group I: V940 + PembrolizumabExperimental Treatment2 Interventions
Participants will receive V940 1 mg via intramuscular (IM) injection every 3 weeks (Q3W) for up to 9 doses plus Pembrolizumab 400 mg via an intravenous (IV) infusion every 6 weeks (Q6W) for 9 cycles (up to \~54 weeks). Each cycle is 6 weeks.
Group II: Placebo + PembrolizumabActive Control2 Interventions
Participants will receive placebo as an IM injection Q3W for up to 9 doses plus Pembrolizumab 400 mg via an IV infusion Q6W for 9 cycles (up to \~54 weeks). Each cycle is 6 weeks.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fox Chase Cancer Center ( Site 0111)Philadelphia, PA
BC Cancer Vancouver ( Site 0005)Vancouver, Canada
Yale-New Haven Hospital-Yale Cancer Center ( Site 0102)New Haven, CT
Duke Cancer Institute ( Site 0106)Durham, NC
More Trial Locations
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Who Is Running the Clinical Trial?
Merck Sharp & Dohme LLCLead Sponsor
ModernaTX, Inc.Industry 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.
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.
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.
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.
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.
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).
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.
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.