PRIMARY OBJECTIVE:~I. To evaluate pathologic complete response (pCR) rates at radical cystectomy (RC) following neoadjuvant erdafitinib with or without atezolizumab in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) and susceptible FGFR3/2.~SECONDARY OBJECTIVES:~I. To determine the rate of pathologic downstaging (=< pT1N0M0) among patients who receive RC.~II. To determine the clinical complete response (cCR) rate in patients who do not undergo planned RC.~III. To determine pCR + cCR. IV. To evaluate 2-year disease-free survival (DFS). V. To evaluate the overall survival (OS) rate at 2 years. VI. To evaluate the safety and tolerability of study treatment as well as surgical complications in the RC group.~EXPLORATORY OBJECTIVES:~I. To correlate the reduction of plasma circulating tumor deoxyribonucleic acid (DNA) (ctDNA) during study treatment and the surveillance period with disease outcomes (pCR and cCR, pathologic downstaging, 2-year DFS and OS).~II. To correlate tumor response with baseline tissue, ctDNA FGFR3/2 mutation status, and molecular signature.~III. To characterize the baseline tumor tissue immune profile of FGFR3/2-aberrant tumors including programmed death-ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and T cell infiltration (PD-L1 expression, peripheral blood mononuclear cell (PBMC), T cell receptor [TCR] repertoire).~IV. To characterize the changes in the above tumor tissue immune profile following study treatment.~V. To correlate baseline tumor tissue TMB with disease outcomes (pCR and cCR, pathologic downstaging, 2-year DFS and OS).~OUTLINE: Patients are randomized to 1 of 2 arms.~ARM I: Patients receive erdafitinib orally (PO) on study. Patients undergo collection of blood on study and during follow-up. Patients also undergo computed tomography (CT)/magnetic resonance imaging (MRI) throughout the trial and cystoscopy during screening and follow-up.~ARM II: Patients receive erdafitinib PO and atezolizumab intravenously (IV) on study. Patients undergo collection of blood on study and during follow-up. Patients also undergo CT/MRI throughout the trial and cystoscopy during screening and follow-up.
This phase II trial test whether erdafitinib with or without atezolizumab works in treating patients with bladder cancer that invades the muscular wall of the bladder and has a change or alteration in a specific gene called the FGFR. This alteration of the FGFR gene causes bladder cancer cells to grow and divide abnormally. The usual treatment for someone with bladder cancer invading the muscular wall is chemotherapy with a drug called cisplatin. However, half of the patients cannot get cisplatin due to safety concerns. Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. 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 the combination of erdafitinib and atezolizumab may help to shrink tumor cells at the time of surgery more than treatment with erdafitinib alone.