Enfortumab Vedotin + Pembrolizumab for Advanced Bladder Cancer
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Emory University
Must not be taking: Investigational agents, High-dose steroids
Disqualifiers: Neuroendocrine histology, Uncontrolled diabetes, Active CNS metastases, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial tests how well enfortumab vedotin (EV) and pembrolizumab works in treating patients with bladder cancer of variant histology (a group of less common types of bladder cancer) that have spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving enfortumab vedotin and pembrolizumab may kill more tumor cells in patients with locally advanced or metastatic bladder cancer of variant histology.
Do I need to stop my current medications to join the trial?
The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving systemic antimicrobial treatment for an active infection or high dose steroids, or if you have had chemotherapy or radiotherapy within 4 weeks prior to entering the study.
What data supports the effectiveness of the drug combination Enfortumab Vedotin and Pembrolizumab for advanced bladder cancer?
Enfortumab Vedotin has been approved by the FDA for treating advanced urothelial cancer, showing a 44% response rate in patients who had prior treatments. Additionally, both Enfortumab Vedotin and Pembrolizumab have individually shown benefits in similar cancer settings, suggesting their combination could be effective.
12345Is the combination of Enfortumab Vedotin and Pembrolizumab safe for humans?
Enfortumab Vedotin has been shown to have a tolerable safety profile in patients with advanced bladder cancer, but it can cause serious side effects like high blood sugar, nerve damage, eye problems, skin reactions, and risks to unborn babies. Pembrolizumab, used in combination, is generally safe but can also have side effects, so it's important to discuss these with your doctor.
12467How is the drug combination of Enfortumab Vedotin and Pembrolizumab unique for advanced bladder cancer?
This drug combination is unique because it combines Enfortumab Vedotin, which targets cancer cells directly, with Pembrolizumab, an immune therapy that helps the body's immune system fight cancer. This combination is particularly beneficial for patients who cannot use standard cisplatin-based chemotherapy, offering a new first-line treatment option for advanced bladder cancer.
12345Eligibility Criteria
Adults with advanced or metastatic bladder cancer of variant histology, who are fit (ECOG <=1), have not had recent treatments that could interfere, and can provide tumor samples. Women must not be pregnant and all participants must agree to use contraception. Exclusions include certain other cancers, uncontrolled illnesses, prior EV or PD-1/PD-L1 inhibitor treatment, active infections like hepatitis B/C, autoimmune diseases requiring systemic treatment within 2 years.Inclusion Criteria
The doctor believes you will live for at least 12 more weeks.
My bladder cancer is of a specific type, not the usual kind.
I finished all my cancer treatments at least 4 weeks ago.
+13 more
Exclusion Criteria
I have not had serious heart problems like heart failure or unstable angina in the last 6 months.
I have moderate to severe numbness, tingling, or muscle weakness.
I have diabetes with an HbA1c level of 7% or higher and symptoms like frequent urination or thirst.
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive enfortumab vedotin and pembrolizumab intravenously. They also undergo CT scan or MRI, and collection of blood throughout the trial.
Up to 2 years
Regular visits for IV administration and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing the combination of Enfortumab Vedotin (EV) and Pembrolizumab in treating less common types of bladder cancer that has spread. EV targets nectin-4 on cancer cells to deliver a drug that kills them; Pembrolizumab helps the immune system fight cancer.
1Treatment groups
Experimental Treatment
Group I: Treatment (enfortumab vedotin, pembrolizumab)Experimental Treatment6 Interventions
Patients receive enfortumab vedotin IV and pembrolizumab IV on study. Patients also undergo CT scan or MRI, and collection of blood throughout the trial.
Enfortumab Vedotin is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Padcev for:
- Locally advanced or metastatic urothelial cancer
🇪🇺 Approved in European Union as Padcev for:
- Locally advanced or metastatic urothelial cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Emory Saint Joseph's HospitalAtlanta, GA
Emory University Hospital/Winship Cancer InstituteAtlanta, GA
Grady Health SystemAtlanta, GA
Emory University Hospital MidtownAtlanta, GA
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Who Is Running the Clinical Trial?
Emory UniversityLead Sponsor
National Cancer Institute (NCI)Collaborator
Seagen Inc.Industry Sponsor
Astellas Pharma IncIndustry Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab. [2023]This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder.
FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. [2022]On December 18, 2019, the FDA granted accelerated approval to enfortumab vedotin-ejfv (PADCEV; Astellas and Seattle Genetics) for treatment of patients with locally advanced or metastatic urothelial cancer who have previously received a programmed cell death protein 1 or programmed death ligand 1 inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. Substantial evidence of effectiveness for this application is obtained from Cohort 1 of the single-arm, multicenter Study EV-201. Patients received enfortumab vedotin (EV) 1.25 mg/kg (up to a maximum dose of 125 mg) intravenously on days 1, 8, and 15 of 28-day cycles until disease progression or unacceptable toxicity. Confirmed objective response rate in the 125-patient efficacy population determined by blinded independent central review was 44% [95% confidence interval (CI), 35.1-53.2], with complete responses in 12%. Median response duration was 7.6 months (95% CI, 6.3-not estimable). Grade 3-4 adverse reactions occurred in 73% of patients. Hyperglycemia, peripheral neuropathy, ocular disorders, skin reactions, infusion site extravasations, and embryo-fetal toxicity are labeled as warnings and precautions for EV. The article summarizes the data and the FDA thought process supporting accelerated approval of EV. This approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study. [2023]Enfortumab vedotin (EV) was approved for advanced urothelial carcinoma (UC) in 2021 after the EV-301 trial showed its superiority to non-platinum-based chemotherapy as later-line treatment after platinum-based chemotherapy and immune checkpoint inhibitors including pembrolizumab. However, no study has compared EV with rechallenging platinum-based chemotherapy (i.e., "platinum rechallenge") in that setting.
FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. [2023]The FDA approved enfortumab vedotinejfv (Padcev)-the first drug to treat adult patients with locally advanced or metastatic urothelial cancer who have received prior treatment with a programmed cell death protein 1 (PD-1)/ programmed cell death ligand 1(PD-L1) inhibitor and platinum-containing chemotherapy.
Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. [2023]Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.
Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. [2021]To evaluate the pharmacology, pharmacokinetics, clinical efficacy, safety, dosing, cost, and clinical implications of enfortumab vedotin-ejfv (EV) in the treatment of locally advanced or metastatic urothelial carcinoma (UC).
Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial. [2023]The EV-201 trial (NCT03219333) demonstrated a clinically meaningful and durable response rate and a tolerable safety profile with enfortumab vedotin (EV) in patients with locally advanced/metastatic urothelial carcinoma (LA/mUC) treated with prior PD-1/PD-L1 inhibitor therapy and platinum-containing chemotherapy (cohort 1). Patient-reported outcome (PRO) measures were included in EV-201 as exploratory endpoints.