Balversa (erdafitinib)

P2, N=239, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2026 --> Mar 2027

Survey-based opinions can effectively capture treatment selection preferences for mUC and could inform future clinical trial design. Additional data, including the impact of residual toxicity from 1L EVP, are needed to better understand real-world treatment sequencing patterns.

Accordingly, gemcitabine-cisplatin with nivolumab and platinum-based chemotherapy followed by maintenance avelumab remain validated evidence-based alternatives, particularly for cisplatin-eligible patients or in regions where enfortumab vedotin plus pembrolizumab is not readily accessible...Enfortumab vedotin monotherapy retains activity post-platinum and immune checkpoint inhibition, erdafitinib provides a targeted benefit in fibroblast growth factor receptor 3-altered tumors, and trastuzumab deruxtecan has emerged as a later-line option for HER2-positive disease. In parallel, circulating tumor DNA is an emerging biomarker with potential to individualize sequencing strategies, although its clinical application remains investigational. This review synthesizes current evidence and highlights practical considerations, emphasizing the need to balance therapeutic innovation with cost effectiveness, equitable access, and global applicability, while identifying critical research priorities in the post-enfortumab vedotin plus pembrolizumab era.

P2, N=1376, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> Jan 2027

First-line erdafitinib monotherapy and erdafitinib plus cetrelimab demonstrated antitumor activity and a manageable safety profile in cisplatin-ineligible patients with mUC.

Recent development of selective FGFR inhibitors-such as pemigatinib, erdafitinib, and futibatinib-has translated mechanistic insights into measurable clinical benefits in genomically defined patient populations. This review also highlights emerging therapeutic modalities, such as antibody-drug conjugates and nanotechnology-based delivery systems, which may improve target specificity and prolong therapeutic durability. By integrating molecular, translational, and clinical evidence, this review aims to establish a comprehensive framework for precision oncology strategies targeting FGFR-driven malignancies.

Herein, we designed and synthesized a series of dual-functional compounds by conjugating the oxygen-mimicking moiety 2-methyl-5-nitroimidazole with the FGFR inhibitor Erdafitinib...These combined effects thereby enhanced tumor sensitivity to radiotherapy. Collectively, the findings support 19e as a potential therapeutic agent for the treatment of malignant tumors.

Pooled analyses confirm the robust efficacy of erdafitinib in a diverse population of pretreated patients with advanced/metastatic CCA harboring prespecified FGFR alterations. These findings are consistent with previously observed efficacy of FGFR-targeted agents in patients with CCA.

Recent advances in targeted therapies, including FGFR inhibitors (for example, erdafitinib) and antibody‑drug conjugates (ADCs) targeting Nectin‑4 (enfortumab vedotin) and HER2 (disitamab vedotin), have reshaped treatment paradigms. The present review synthesizes current evidence on molecularly guided therapies, contrasts resistance mechanisms between FGFR inhibitors and ADCs, and evaluates strategies to overcome therapeutic limitations. By integrating translational insights and emerging preclinical data, it was aimed to provide a roadmap for optimizing biomarker‑driven approaches, novel combinations and next‑generation agents for the treatment of UC.

P2, N=90, Recruiting, Spanish Oncology Genito-Urinary Group | Trial completion date: Mar 2029 --> Oct 2029 | Trial primary completion date: Mar 2026 --> Jul 2026

Enfortumab vedotin, a Nectin-4 targeting ADC, is now the first line therapy of choice in combination with pembrolizumab. Erdafitinib, a pan FGFR1-4 inhibitor, is approved for patients with susceptible FGFR3 alterations...We propose strategies for overcoming resistance including combination strategies, tumor microenvironment modification, and drug structure modification to maximize efficacy. The progress to date in mUC has been remarkable, but there is still significant work to do in this deadly disease and this review highlights the gap between current available therapeutics and cure that so desperately needs to be closed.

Alterations in FGFR3, commonly found in the luminal-papillary molecular subtype associated with low response to immunotherapy, are the target of erdafitinib. Enfortumab vedotin, which targets Nectin-4 (expressed in >95% of urothelial carcinomas), is approved for patients who progress after chemotherapy and/or immunotherapy...Sacituzumab govitecan, an antibody-drug conjugate directed against Trop-2, is effective in basal, luminal and stroma-rich subtypes but not in neuroendocrine carcinomas. In addition, therapies developed for HER2-positive breast cancer have shown efficacy in urothelial carcinoma, with recent data from the DESTINY pan-tumour phase II trial leading to FDA approval of trastuzumab deruxtecan for HER2-overexpressing metastatic urothelial carcinoma. This paper is a comprehensive review of the molecular pathology of bladder cancer, highlighting advances in molecular classification, biomarkers and personalized therapies. The transition from morphology-based classifications to combined morphological and molecular approaches, with therapeutic implications, is also addressed.