Testing Anti-Cancer Drugs Erdafitinib With or Without Atezolizumab in Patients With Localized Bladder Cancer Not Able to Receive Cisplatin Chemotherapy, NERA Trial

NCT05564416 | Withdrawn Phase 2 FDA Drug

• 3 other identifiers: NCI-2022-0806210517UM1CA186644
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial compares the effect of erdafitinib alone to using the combination of erdafitinib and atezolizumab in treating patients with bladder cancer whose tumor invades the muscular bladder wall (muscle invasive)and who are ineligible for treatment with a chemotherapy drug called cisplatin. This trial also determines whether these treatment approaches are better than the usual approach for treating this type of cancer. The usual approach for treatment of someone with muscle invasive bladder cancer is chemotherapy with a drug called cisplatin followed by surgery (most common), or chemoradiation (radiation combined with chemotherapy) to the bladder (in some patients). However, half of the patients cannot get cisplatin due to safety concerns. This study has a screening step. The purpose of this step is to test patient's tumor to find out if it has a specific change (alteration) in the fibroblast growth factor receptor (FGFR) gene to determine patient's eligibility for this trial. Alteration of the FGFR gene causes bladder cancer cells to grow and divide abnormally. Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein. This may help keep cancer cells from growing and may kill them. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving erdafitinib alone or in combination with atezolizumab may help to shrink tumor cells at the time of surgery better than the usual treatment in muscle invasive bladder cancer.

Conditions

Bladder Carcinoma; Bladder Urothelial Carcinoma; Muscle Invasive Bladder Carcinoma; Renal Pelvis and Ureter Urothelial Carcinoma; Stage II Bladder Cancer AJCC v8; Stage III Bladder Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR)

  Will be compared between the two arms using one-sided Z test with unpooled variance. Proportions with 95% confidence intervals will be provided for the two treatment arms. To avoid potential bias, the primary analysis will include all randomized, eligible patients even if they do not receive treatment.

  Up to 2 years

Secondary Outcomes (6)

• Rate of pathologic downstaging (=< pT1N0M0) among all patients who receive radical cystoscopy (RC)

  Time until death due to bladder, assessed up to 2 years

• Clinical complete response (cCR) rate among patients who do not undergo RC

  At week 10

• Pathologic complete response (pCR) + clinical complete response (cCR) rate

  At week 10

• Disease-free survival (DFS)

  Time until death due to bladder cancer, assessed up to 2 years

• Overall survival (OS) rate

  Time from treatment start date until death, assessed at 2 years

Other Outcomes (4)

• FGFR 3/2 alteration type (mutation versus [vs.] fusion)

  Up to 2 years

• FGFR signature

  Up to 2 years

• Clinical staging (cT2N0 vs. cT3/T4 or N)

  Up to 2 years

Study Arms (2)

Arm I (erdafitinib)

EXPERIMENTAL

Patients receive erdafitinib orally (PO). Patients undergo collection of blood and computed tomography (CT)/magnetic resonance imaging (MRI) at various time points throughout the trial and colposcopy at baseline.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Cystoscopy; Drug: Erdafitinib; Procedure: Magnetic Resonance Imaging

Arm II (erdafitinib, atezolizumab)

EXPERIMENTAL

Patients receive erdafitinib PO and atezolizumab intravenously (IV). Patients undergo collection of blood and CT/MRI at various time points throughout the trial and colposcopy at baseline.

Biological: Atezolizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Cystoscopy; Drug: Erdafitinib; Procedure: Magnetic Resonance Imaging

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Arm II (erdafitinib, atezolizumab)

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (erdafitinib); Arm II (erdafitinib, atezolizumab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm I (erdafitinib); Arm II (erdafitinib, atezolizumab)

Cystoscopy PROCEDURE

Undergo cystoscopy

Also known as: CS

Arm I (erdafitinib); Arm II (erdafitinib, atezolizumab)

Erdafitinib DRUG

Given PO

Also known as: Balversa, JNJ 42756493, JNJ-42756493, JNJ42756493

Arm I (erdafitinib); Arm II (erdafitinib, atezolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm I (erdafitinib); Arm II (erdafitinib, atezolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have muscle-invasive disease, tumor stage T2-T4, N0-1, based on transurethral resection of bladder tumor (TURBT) performed within 8 weeks prior to enrollment
• Clinical stage T2-T4, N0 or N1, M0 by CT chest abdomen pelvis (or CT chest and MRI abdomen pelvis). Ultrasound, fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET), and plain x-rays are not acceptable methods of evaluating clinical staging in the absence of CT or MRI scans

You may not qualify if:

• Patients must be eligible and planned for curative-intent RC, as determined by a urologic oncologist
• Patients who are ineligible for or decline cisplatin-based chemotherapy.
• Cisplatin-ineligibility defined as \>= 1 of the following criteria (modified from the Galsky criteria): Eastern Cooperative Oncology Group (ECOG) performance status (PS) of \>= 2, either estimated or measured creatinine clearance (CrCl) or glomerular filtrate rate (GFR) \< 60 mL/min, Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 grade \>= 2 audiometric hearing loss or grade \>= 2 peripheral neuropathy
• For cisplatin-eligible patients who decline cisplatin-based neoadjuvant chemotherapy (NAC), the subject's refusal for cisplatin must be clearly documented. Subjects must be informed that cisplatin-based NAC can improve cure rates, and it is unknown whether FGFR3/2 aberrant MIBC have better cure rates with neoadjuvant erdafitinib than cisplatin-based NAC
• Patients with susceptible FGFR3/2 alterations, based on tumor tissue testing, or blood ctDNA testing, performed by the local institution. (Given presence of intratumoral heterogeneity in FGFR3 status, a sample of the deeper part of the invasive tumor is preferred for tissue FGFR screening using baseline TURBT sample)
• FGFR3 gene mutations (R248C, S249C, G370C, Y373C) or FGFR gene fusions (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7), as defined by the current Food and Drug Administration (FDA) indication for erdafitinib, determined by a laboratory certified by Clinical Laboratory improvement Amendments (CLIA). The principal investigator (PI) will review all clinical testing report to confirm eligibility
• The FGFR screening assay is chosen by the local investigators depending on what is available (FoundationOne CDx, TSO500, Therascreen or others). If local FGFR screening capabilities are not available, study team may be able to provide funding support
• FGFR status will be confirmed centrally and retrospectively using whole exome sequencing (WES) and ribonucleic acid (RNA) sequencing at the National Clinical Laboratory Network (NCLN) genomics lab, however patients can proceed with randomization and study treatment prior to confirmation testing results being made available
• Patients with the following prior therapies are allowed:
• PD-1/PD-1 immune checkpoint inhibitors (ICIs) for non-muscle invasive bladder cancer (NMIBC) is allowed if last dose was given \>1 year prior to randomization
• Hormone-replacement therapy or oral contraceptives
• Herbal therapy \>1 week prior to cycle 1, day 1 (herbal therapy intended as anti-cancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)
• Age \>= 18 years; because no dosing or adverse event data are currently available on the use of erdafitinib in combination with atezolizumab in patients \< 18 years of age, children are excluded from this study
• ECOG performance status =\< 2 (Karnofsky \>= 60%)
• Absolute neutrophil count \>= 1,500/mcL (without granulocyte colony stimulating factor support) (within 14 days of study registration)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

atezolizumab; Specimen Handling; Cystoscopy; erdafitinib; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Endoscopy; Diagnostic Techniques, Surgical; Diagnostic Techniques, Urological; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Di Maria Jiang

  University Health Network Princess Margaret Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2022
• First Posted: October 3, 2022
• Study Start: October 12, 2023
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share