Podcast on the Emerging Role of PD-(L)1/VEGF Bispecific Antibodies in the Evolving Advanced Renal Cell Carcinoma Treatment Landscape

Combinations of an immune checkpoint inhibitor (ICI) + anti-programmed cell death 1 protein (PD-1) or anti-programmed cell death ligand 1 (PD-L1) or an ICI + tyrosine kinase inhibitor (TKI; anti-vascular endothelial growth factor [VEGF]) are the current standard first-line treatments for advanced renal cell carcinoma (RCC). However, novel therapies are needed as treatments for RCC have relied on the same mechanisms for decades, with only modest advancements made in the field compared with other genitourinary diseases. Therefore, a considerable unmet need remains for additional treatment options with enhanced activity and minimal toxicity for patients with advanced RCC. Simultaneous bispecific targeting of PD-1 and VEGF may improve efficacy and safety compared with combination therapy of PD-1- and VEGF-targeting single agents. In this podcast, authors discuss the evolving treatment landscape for patients with RCC and describe how bispecific antibodies, as monotherapy or combination therapy, have the potential to transform the treatment of these patients. Preclinical evidence shows that bispecific co-targeting of PD-(L)1 and VEGF may result in cooperative binding, which can enhance both PD-1 binding affinity and anti-angiogenic activity. Bispecific targeting can also potentially confer safety advantages owing to a reduction in immune-related adverse events. PD-(L)1/VEGF bispecifics under development include PF-08634404, ivonescimab, and BNT327, all of which have distinct structural configurations and mechanistic differences. These bispecific antibodies, among others, are being evaluated for the treatment of patients with advanced RCC. The authors discuss existing clinical evidence with bispecific antibodies in other cancers and explore the rationale for evaluating the antitumor activity of PD-(L)1/VEGF bispecifics, either as monotherapy or in conjunction with other treatments in patients with RCC.Podcast and Infographic available for this article. Podcast (MP4 107526 KB) Infographic.