Erdafitinib + Enfortumab Vedotin for Bladder Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase Ib trial evaluates the best dose, potential benefits, and/or side effects of erdafitinib in combination with enfortumab vedotin in treating patients with bladder cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and possesses genetic alterations in FGFR2/3 genes. Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals cancer cells to multiply. This may help keep cancer cells from growing and may kill them. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. 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. Giving erdafitinib in combination with enfortumab vedotin may shrink or stabilize metastatic bladder cancer with alterations in FGFR 2/3 genes.
Do I need to stop my current medications for the trial?
The trial does not specify if you need to stop your current medications, but it does mention that patients taking strong inhibitors or inducers of CYP3A are ineligible. It's important to discuss your current medications with the trial team to ensure there are no interactions.
What data supports the effectiveness of the drug Enfortumab Vedotin for bladder cancer?
Enfortumab Vedotin has been shown to be effective for patients with advanced bladder cancer who have already tried other treatments. In a study, 44% of patients responded to the drug, with some experiencing complete disappearance of their cancer, and the effects lasted for an average of 7.6 months.
12345What safety information is available for Erdafitinib and Enfortumab Vedotin in treating bladder cancer?
Enfortumab Vedotin, also known as Padcev, has been approved for treating 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. In studies, 73% of patients experienced severe side effects, and skin reactions were common, affecting up to 47% of patients.
13467What makes the drug combination of Erdafitinib and Enfortumab Vedotin unique for bladder cancer?
This drug combination is unique because Enfortumab Vedotin is a first-in-class antibody-drug conjugate that targets Nectin-4 on bladder cancer cells, delivering a toxin to kill the cells, while Erdafitinib is a tyrosine kinase inhibitor that targets specific proteins involved in cancer cell growth. This combination offers a novel approach for patients who have limited options after standard treatments like chemotherapy and immunotherapy.
12358Eligibility Criteria
This trial is for adults with metastatic bladder cancer that has spread and worsened after chemotherapy and immunotherapy. Participants must have specific genetic changes (FGFR2/3), adequate organ function, no major health issues, and agree to use contraception. Excluded are those who've had certain recent treatments or surgeries, uncontrolled illnesses, prior FGFR inhibitor treatment, or strong reactions to similar drugs.Inclusion Criteria
My cancer got worse after treatment with platinum drugs and immune therapy.
My cancer has FGFR2/3 changes confirmed by a specific blood or tissue test.
I had hepatitis C but have been treated and cured.
My bladder cancer returned within a year after completing platinum-based therapy.
I have had an eye exam and do not have any active eye diseases.
My cancer is advanced bladder cancer confirmed by lab tests.
My kidney function, measured by creatinine clearance, is normal or only slightly reduced.
My cancer has a mainly transitional cell pattern.
I've had platinum-based treatment for advanced or inoperable lung cancer.
My hepatitis B virus is under control with treatment.
I can take care of myself but might not be able to do heavy physical work.
I am 18 years old or older.
Exclusion Criteria
I have a history of eye conditions that could increase the risk of eye side effects.
I have been treated with an FGFR inhibitor before.
I have not had radiotherapy in the last 2 weeks.
I am not taking any strong medication that affects liver enzymes.
I have not had another invasive cancer in the last 3 years.
My diabetes is not under control.
I am not currently being treated for an active infection.
I have previously been treated with enfortumab vedotin or similar drugs.
I have a history of or currently have uncontrolled heart problems.
Participant Groups
The trial tests a combination of two drugs: Erdafitinib (a kinase inhibitor blocking abnormal protein signals in cancer cells) and Enfortumab Vedotin (an antibody-drug conjugate targeting nectin-4 on cancer cells). The study aims to find the best dose and assess benefits/side effects for patients with genetic alterations in FGFR2/3 genes.
1Treatment groups
Experimental Treatment
Group I: Treatment (erdafitinib, enfortumab vedotin)Experimental Treatment7 Interventions
Patients receive erdafitinib PO QD on days 1-28 of each cycle and enfortumab vedotin IV over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and blood sample collection throughout the trial and may undergo echocardiography or MUGA scan during screening and bone scan throughout the study.
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:
University Health Network Princess Margaret Cancer Center LAOToronto, Canada
University of Colorado HospitalAurora, CO
Los Angeles County-USC Medical CenterLos Angeles, CA
UT Southwestern/Simmons Cancer Center-DallasDallas, TX
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
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: Nursing Perspectives on the Management of Adverse Events in Patients With Locally Advanced or Metastatic Urothelial Carcinoma. [2021]Many patients with locally advanced or metastatic urothelial carcinoma (mUC) need additional treatment options beyond PD-1 or PD-L1 inhibitors and platinum-based chemotherapies. Enfortumab vedotin-ejfv (EV) is an antibody-drug conjugate directed at Nectin-4 that received accelerated approval for treatment of adults with locally advanced or mUC previously treated with PD-1/PD-L1 inhibitors and platinum- containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic settings.
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-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).
Enfortumab vedotin-ejfv for the treatment of advanced urothelial carcinoma. [2022]Metastatic urothelial carcinoma is an aggressive malignancy with a poor prognosis. Research in recent years has led to the approval of new treatments that offer improved survival for patients. Enfortumab vedotin-ejfv is a first-in-class monoclonal antibody drug conjugate that binds Nectin-4, a protein expressed on bladder cancer cells, and delivers the tubulin toxin, monomethyl auristatin E, into the cell causing cell death. Enfortumab vedotin-ejfv has changed the standard of care treatment in urothelial carcinoma with a high response and disease-control rate, acceptable toxicity profile and improved overall survival for patients who previously had limited options after failure of chemotherapy and/or immunotherapy.
Outcomes of metastatic urothelial carcinoma following discontinuation of enfortumab-vedotin. [2022]Enfortumab vedotin (EV) is approved to treat metastatic urothelial carcinoma (mUC) following platinum and PD1/L1 inhibitors. Since the outcomes and patterns of therapy of patients following discontinuation of EV are unknown, we conducted a retrospective study to assess this issue.
Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. [2023]Enfortumab vedotin is a novel drug for locally advanced or metastatic urothelial carcinoma, but it is associated with a high incidence of skin reactions (up to 47.0%).
A translational model-based approach to inform the choice of the dose in phase 1 oncology trials: the case study of erdafitinib. [2022]Erdafitinib (JNJ-42756493, BALVERSA) is a tyrosine kinase inhibitor indicated for the treatment of advanced urothelial carcinoma. In this work, a translational model-based approach to inform the choice of the doses in phase 1 trials is illustrated.