Bavencio (avelumab)

P3, N=205, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Feb 2027 --> Aug 2026 | Trial primary completion date: Feb 2027 --> Aug 2026

P1, N=210, Active, not recruiting, iOnctura | Trial completion date: Mar 2025 --> Mar 2027

P1/2, N=19, Active, not recruiting, Melanoma and Skin Cancer Trials Limited | Recruiting --> Active, not recruiting | Trial completion date: Jul 2027 --> Dec 2027 | Trial primary completion date: Jul 2027 --> Dec 2026

Among the synthesized series, compound 8g exhibited the highest potency, with IC₅₀ values of 3.93 μM, 9.56 μM, and 6.30 μM against HepG2, PC-3, and HCT-116, respectively, surpassing the reference drugs doxorubicin (4.50 μM against HepG2) and sorafenib (9.18 μM against HepG2). Mechanistically, 8g demonstrated strong inhibition of VEGFR2 (IC₅₀ = 0.38 μM), but it outperformed PD-L1 inhibition compared to Bavencio (IC₅₀ = 134.41 pg/mL and 217.74 pg/mL, respectively)...In silico molecular docking and dynamic simulation assisted data strongly correlated with the experimental approach that compound 8g exerts multi-targeted anticancer activity via VEGFR2 and PD-L1 inhibition. In conclusion, 8g is a promising candidate recommended for further therapeutic development.

P2, N=32, Recruiting, Centre Hospitalier Universitaire de Besancon | Not yet recruiting --> Recruiting

P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Sep 2026

Over the past decade, multiple ICIs have demonstrated meaningful clinical activity, and their indications have expanded across treatment lines, including second-line therapy after platinum, first-line therapy for cisplatin-ineligible disease, avelumab maintenance following chemotherapy, and, more recently, combination strategies such as pembrolizumab plus enfortumab vedotin. In this review, we provide a comprehensive overview of currently established and emerging biomarkers of ICI response in UBC, including PD-L1 immunohistochemistry, serum inflammatory markers, tumor mutational burden, histology and molecular subtypes, gene expression patterns and microbiome features. We discuss their strengths, limitations, and potential translational relevance, highlighting ongoing challenges and future directions.

P1, N=9, Completed, TILT Biotherapeutics Oy | Active, not recruiting --> Completed

P1, N=19, Active, not recruiting, University of Oklahoma | Trial completion date: Feb 2026 --> Oct 2026

Isoform-specific knockdown of TTLL12 and HM13 significantly decreased the viability of two EAC cell lines, sensitized EAC cell lines to standard-of-care chemotherapy agents (paclitaxel and carboplatin) with synergy, and inhibited EAC cell migratory potential. In addition, HM13 isoform knockdown increased the response to an anti-PD-L1 agent, avelumab, in EAC cells, suggesting a role for isoform switching in immunosuppression. Taken together, study results suggest that isoform switching may provide novel insight for the identification of prognostic markers and inform new potential therapeutic targets for EAC treatment or prevention.

P2, N=144, Not yet recruiting, Gruppo Oncologico Italiano di Ricerca Clinica

Two and a half years later, a solitary pelvic nodal recurrence achieved complete response to gemcitabine-cisplatin, after which avelumab maintenance was started. He remains recurrence-free for three years without immune-related adverse events. Durable remission with pembrolizumab following progression on avelumab suggests that switching from PD-L1 to PD-1 blockade can overcome resistance in selected patients; prospective studies and biomarker strategies, including PD-L2 assessment, are warranted and may guide individualized rechallenge strategies.