ESMO 2024 – Astra’s B7-H4 effort underwhelms

After three years in a phase 1/2 solid tumour trial, data have finally emerged on AstraZeneca’s B7-H4 ADC puxitatug samrotecan and they look – at best – in line with results from similarly acting agents. There are caveats: the study, in heavily pretreated ovarian, breast and endometrial cancers, and cholangiocarcinoma, only enrolled patients with B7-H4 expression of 25% or higher, which might have been expected to bolster efficacy. In addition there were two responses at 3.2mg/kg, which also saw two dose-limiting toxicities, and Astra is now focused on 1.6-2.4mg/kg. There was also one fatal case of interstitial lung disease, at 1.6mg/kg. As well as monotherapy dose expansion, a combination with Astra’s anti-PD-1 x TIGIT MAb rilvegostomig has begun. One tidbit from the study was that, of 17% patients previously treated with a topoisomerase inhibitor-based ADC, there were no responses. This led the ESMO discussant, Dr Lillian Siu of the Princess Margaret Cancer Centre in Toronto, to ask whether resistance to this payload might be developing; that's a question for future ADC development. In the B7-H4 ADC arena, GSK, via Hansoh, and Pfizer are further ahead, but this field is nowhere near as crowded as B7-H3 – perhaps for good reason.

B7-H4 ADCs in clinical development

Source: OncologyPipeline.