BISCAY is a personalised clinical trial looking at different combinations of AstraZeneca’s Imfinzi (durvalumab) in platinum-refractory urothelial cancer.

In this open-label, randomized, Phase Ib study, patients were recruited who had certain molecular alterations, including fibroblast growth factor receptor (FGFR), homologous recombination repair gene mutation, and mutations in genes involved with cell cycle regulation (for example, loss of either retinoblastoma 1 or cyclin-dependent kinase inhibitor 2A or amplification of cyclin E1 or MYC family genes).

The study is currently testing Imfinzi + AZD4547 (an FGFR inhibitor), Imfinzi + Lynparza (a PARP inhibitor), Imfinzi + vistusertib, and Imfinzi monotherapy. Objective response rates (ORR) were 28.6%, 35.7%, 24.1%, and 27.6%, respectively. Although the combinations showed higher ORRs than the current standard of care, none of them met the pre-specified ORR endpoint of 50%.

More research is warranted

The monotherapy arm had an 8% higher response rate than the control arm, which, according to key opinion leaders, was a plausible result as the monotherapy arm had a different biomarker and could not be directly compared. Even with other combinations, especially with the PARP inhibitor Lynparza, in patients expressing higher PD-L1 levels and tumour mutational burden (TMB), the ORR was a remarkable 35.7% but still warrants more research.

Similarly, in patients with FGFR mutations, the combination of Imfinzi plus AZD4547 showed a subtle difference in ORR when compared to the monotherapy, however, the results have not been established completely and need more research, which was seen as a major shortcoming of the trial.

A biomarker-directed multidrug umbrella trial in metastatic patients is seen as an innovative approach addressing high unmet needs in patients with locally advanced or metastatic bladder cancer. The trial has a complex design and a comprehensive biomarker methodology to look at mutations. The entire approach is seen as a step into the personalized treatment paradigm for bladder cancer.