A new pivotal Nectin-4 player

Until Padcev's approval Nectin-4 was a target without extensive biopharma development activity, but it now comprises four pivotal-stage projects. The latest to enter the fray is Jiangsu HengRui, whose ADC SHR-A2102 entered a phase 3 study in urothelial carcinoma this month, a new entry on the clinicaltrials.gov registry reveals. This aims to enrol 402 patients who have been pretreated with platinum chemo and PD-(L)1 inhibitors, and has OS and PFS versus chemo alone as co-primary endpoints. However, it will apparently be a Chinese, rather than a global, trial. While all the leading anti-Nectin-4 ADCs use an auristatin payload, SHR-A2102 is notable for employing rezetecan, a topoisomerase 1 inhibitor, and the pivotal trial allows patients to have failed on another ADC like Padcev. As such it plays into a recent theme that a cancer can become resistant not only to an ADC's targeting moiety but also to its payload. The phase 3 initiation comes at a tricky time for another Nectin-4 player, Bicycle Therapeutics, whose bicycle-toxin conjugate zelenectide pevedotin has yielded a disappointing response rate, in addition to facing questions over its approvability on an accelerated basis.

Pivotal studies of anti-Nectin-4 ADCs*

Note: *zelenectide pevedotin uses a bicyclic rather than a MAb format. Source: OncologyPipeline.