Testing Combination Erdafitinib and Enfortumab Vedotin in Metastatic Bladder Cancer After Treatment With Chemotherapy and Immunotherapy
Phase Ib Trial of Erdafitinib Combined With Enfortumab Vedotin Following Prior Therapies for Metastatic Urothelial Carcinoma With FGFR2/3 Genetic Alterations
4 other identifiers
interventional
24
2 countries
9
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jul 2022
Longer than P75 for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 14, 2021
CompletedFirst Posted
Study publicly available on registry
July 15, 2021
CompletedStudy Start
First participant enrolled
July 7, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2026
May 13, 2026
March 1, 2026
4.4 years
July 14, 2021
May 12, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Incidence of adverse events
Up to 2 years
Recommended phase II dose
Up to 28 days
Maximum tolerated dose of enfortumab vedotin
The highest dose of enfortumab vedotin in combination with fixed dose erdafitinib that does not cause unacceptable side effect.
Up to 28 days
Secondary Outcomes (4)
Overall response rate
Up to 2 years from study enrollment
Duration of response
Time from complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years from study enrollment
Progression free survival
Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years
Overall survival
Up to 2 years from study enrollment
Other Outcomes (4)
PD-L1, Nectin-4, FGFR3/phosphor-FGFR3, cell lineage and progression marker expression
Up to 2 years from study enrollment
Tumor subtyping, tumor microenvironment, and mutations associated with treatment response
Up to 2 years from study enrollment
Mechanisms of resistance and response
Up to 2 years from study enrollment
- +1 more other outcomes
Study Arms (1)
Treatment (erdafitinib, enfortumab vedotin)
EXPERIMENTALPatients 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.
Interventions
Undergo blood sample collection
Undergo CT
Undergo echocardiography
Given IV
Given PO
Undergo MUGA scan
Undergo bone scan
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically documented locally advanced (T4b, any N; or any T, N 2-3) or metastatic (M1, Stage IV; or metastatic recurrence after locoregional treatment) urothelial carcinoma (including renal pelvis, ureters, urinary bladder, urethra). Patients with mixed histologies are required to have a dominant transitional cell pattern
- Patients who had disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin \[GC\], methotrexate, vinblastine, doxorubicin and cisplatin \[MVAC\], carboplatin and gemcitabine \[Carbo-Gem\]) and an immune checkpoint inhibitor (PD-1/ PD-L1 inhibitor including but not limited to: atezolizumab, pembrolizumab, durvalumab, avelumab, and nivolumab)
- Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease
- Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive UC, with recurrence/progression =\< 12 months following completion of therapy
- Patients who received immune checkpoint inhibitor therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 12 months of therapy completion are eligible. This criterion does not apply if the checkpoint inhibitor is contraindicated
- Patients with metastatic urothelial carcinoma who are cisplatin-ineligible and progressed on upfront immune checkpoint inhibitor; or ineligible/refused immune checkpoint inhibitor therapy will be eligible for this trial
- Patient who received prior antibody drug conjugate such as sacituzumab govitecan are allowed
- Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Previously irradiated lesions cannot be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions
- Patients must have FGFR2/3 activating alterations identified by tumor tissue or plasma ctDNA profiling using a Clinical Laboratory Improvement Act (CLIA) certified College of American Pathologists (CAP) accredited platform
- Age \>= 18 years, for ability to comply with protocol
- Because no dosing or adverse event data are currently available on the use of erdafitinib in combination with enfortumab vedotin in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Absolute neutrophil count \>= 1,500/mcL (within 14 days prior to beginning trial treatment)
- Platelets \>= 100,000/mcL (within 14 days prior to beginning trial treatment)
- Hemoglobin \>= 9 g/dL (within 14 days prior to beginning trial treatment)
- +14 more criteria
You may not qualify if:
- Patients who have had chemotherapy, targeted therapies, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (including ongoing sensory or motor neuropathy of grade 2 or higher) (i.e., have residual toxicities \> grade 1 or returned to baseline) with the exception of alopecia. Subjects with =\< grade 2 immunotherapy- related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of hormone replacement therapy (if indicated). Subjects with ongoing \>= grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Subjects with ongoing immunotherapy related colitis, uveitis, myocarditis, or pneumonitis or subjects with other immunotherapy related adverse events (AEs) requiring high doses of steroids (\> 20 mg/day of prednisone or equivalent) are excluded
- Patients who have previously received enfortumab vedotin or other MMAE-based ADCs
- Patients who have had prior treatment with an FGFR inhibitor
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to erdafitinib and enfortumab vedotin
- Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- Patients with a history of any corneal or retinal abnormality likely to increase the risk of eye toxicity
- Patients with uncontrolled intercurrent illness and currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of starting treatment. Routine antimicrobial prophylaxis is permitted
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
- Subjects who have received radiotherapy within 2 weeks prior to start of treatment. Subject must have recovered adequately from the toxicity from the intervention prior to starting study treatment
- Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) \>= 8% or HbA1c 7% to \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
- Subjects who have received major surgery within 4 weeks prior to start of treatment. Subject must have recovered adequately from complications from the intervention prior to starting study treatment
- Subjects who have received a prior allogeneic stem cell or solid organ transplant
- Has persistent phosphate level \> ULN during screening (within 14 days of treatment and prior to cycle 1 day 1) and despite medical management
- Has a history of or current uncontrolled cardiovascular disease including:
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rohit Jain
University Health Network Princess Margaret Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 14, 2021
First Posted
July 15, 2021
Study Start
July 7, 2022
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2026
Last Updated
May 13, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
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