From BCG to bispecifics: Sara Coca Membribes, MD, on bladder cancer's new era

The bladder cancer treatment landscape is undergoing rapid transformation across both metastatic and non–muscle invasive bladder cancer (NMIBC). In this video interview, recorded at the 41st Annual Congress of the European Association of Urology, Sara Coca Membribes, MD, a medical oncologist clinical research fellow at Barts Health NHS Trust in London, United Kingdom, highlights several emerging therapeutic strategies with near-term clinical implications.

Personalized cancer vaccines. Neoantigen-based vaccines represent a promising frontier, particularly in the adjuvant setting where they target minimal residual disease rather than bulky tumor burden. Early-phase trials are evaluating customized vaccines administered alongside adjuvant immunotherapy, leveraging T-cell–mediated recognition of tumor-specific antigens to mount a durable antitumor response.

VEGF/PD-1 bispecific antibodies. Dual VEGF/PD-1 blockade is attracting interest beyond simple angiogenesis inhibition. Emerging data suggest VEGF plays a meaningful immunosuppressive role in the tumor microenvironment, distinct from its angiogenic effects. Early-phase investigation of a VEGF/PD-1 bispecific agent in urothelial carcinoma is imminent, with multiple analogous agents in development across tumor types.

Antibody-drug conjugates (ADCs). Enfortumab vedotin-ejfv (Padcev) has already established itself as standard of care in the metastatic setting and is now being incorporated into perioperative regimens following positive trials in both cisplatin-eligible and cisplatin-ineligible populations. Attention is now turning to novel ADC combinations and new targets. Particularly notable is izalontamab brengitecan (iza-bren, BL-B01D1), a dual ADC simultaneously targeting EGFR and HER3. Promising early data in pretreated patients have prompted a randomized phase 3 trial comparing this agent against platinum-based chemotherapy.

FGFR3-targeted therapy. Interest in FGFR3 inhibition is resurging, with a frontline triplet regimen now under investigation combining enfortumab vedotin with dabogratinib, a selective FGFR3 inhibitor for patients harboring FGFR3 alterations. This approach raises the prospect of chemotherapy-free frontline treatment within the next decade.

NMIBC: Challenging BCG dominance. Two of three major randomized trials evaluating immune checkpoint inhibitors in BCG-naive NMIBC met their primary end point of event-free survival, although overall survival data require longer follow-up. Patient selection remains a critical challenge, with circulating tumor DNA and urinary tumor DNA emerging as potential biomarkers to identify those most likely to benefit from systemic therapy. Intravesical device-based delivery is also advancing: the gemcitabine intravesical system (Inlexzo, formerly TAR-200) holds FDA labeling for BCG-refractory disease, and a randomized phase 3 trial comparing the gemcitabine intravesical system plus the anti–PD-1 antibody cetrelimab vs the gemcitabine intravesical system alone in BCG-naive NMIBC is forthcoming.