Bladder Cancer (Urothelial) Clinical Trials

About Bladder Cancer (Urothelial) trials

Bladder cancer trial activity centers on stage (non-muscle-invasive vs muscle-invasive vs metastatic), prior platinum and IO exposure, and a small set of actionable molecular targets. PD-L1 (CD274) status is tested but IO is now standard front-line for metastatic urothelial carcinoma, with the post-EV-302 regimen (enfortumab vedotin + pembrolizumab) as the standard first-line option regardless of PD-L1. FGFR3 mutations and fusions occur in 15-20% of urothelial carcinoma and gate eligibility for FGFR inhibitor trials, with erdafitinib already approved for post-platinum FGFR3-altered disease. FGFR4 is less actionable than FGFR3 in bladder cancer but tested for completeness. HER2 (ERBB2) amplification or overexpression in roughly 10-15% of urothelial carcinoma gates anti-HER2 ADC trials, which have shown strong activity. MMR deficiency is uncommon in urothelial carcinoma but qualifies the rare patient for IO trials.

Most current bladder cancer trial activity falls into stage and treatment-line groups. Non-muscle-invasive bladder cancer (NMIBC) trials test BCG-unresponsive strategies (gene therapies, IO, novel intravesical agents), BCG-naive combinations, and bladder-preservation approaches. Muscle-invasive bladder cancer (MIBC) perioperative trials test neoadjuvant IO combinations, adjuvant IO, and chemoradiation strategies for bladder preservation. Metastatic first-line trials center on enfortumab vedotin + pembrolizumab as the new standard, with trials testing additions, alternatives, and post-EV-pembrolizumab strategies. Metastatic later-line trials test FGFR3-targeted agents (next-generation FGFR inhibitors for resistance to first-generation), HER2-amplified ADCs (T-DXd and similar), and novel mechanisms in EV-pretreated patients. FGFR3-altered trials are organized by line and prior FGFR inhibitor exposure. HER2-amplified trials are an active emerging space for the substantial subset of urothelial patients with HER2 expression. Combination trials testing IO with ADCs in earlier lines and post-progression are common.

What bladder cancer trials gate on most often: disease stage, prior platinum chemotherapy, and prior IO and EV exposure. Stage (NMIBC, MIBC, metastatic) determines which trial set applies. Histology (urothelial / transitional cell vs variant histologies like micropapillary, plasmacytoid, sarcomatoid, or pure squamous) gates some trials. Prior platinum chemotherapy and platinum eligibility (cisplatin-eligible vs cisplatin-ineligible by renal function and other criteria) gates many first-line trials. Prior IO exposure for post-IO trials. Prior enfortumab vedotin (EV) exposure has become a defining filter as EV moves to first-line; many later-line trials specify EV-pretreated or EV-naïve. FGFR3 mutation or fusion status for FGFR-targeted trials. Prior FGFR inhibitor exposure (and which generation) for FGFR-targeted trials. HER2 status by IHC or FISH for HER2-targeted trials. Performance status, ECOG 0-2 typical. Renal function (creatinine clearance) is screened on most trials, with cisplatin-based trials requiring CrCl ≥60 mL/min typically.

Biomarkers tested in Bladder Cancer (Urothelial) trials

These are the molecular markers most commonly required or evaluated in Bladder Cancer (Urothelial) eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.