A new SERD in the pivotal pipeline

There's a new oral SERD (selective ER degrader) to challenge the likes of Menarini's Orserdu, Lilly's imlunestrant and Arvinas and Pfizer's vepdegestrant. This is Jiangsu HengRui's HRS-8080, a molecule that's about to enter pivotal development, according to a just revealed clinicaltrials.gov entry. True, its significance might be blunted by the fact that HengRui is Chinese rather than a western company, but HRS-8080 could still be of interest to a US biopharma group keen to get into the SERD space on the back of any rival success in this field. Success in second-line ER-positive HER2-negative breast cancer seems restricted to ESR1-mutated disease, where Orserdu is approved, and to which the activity of other SERDs including vepdegestrant is limited. It's the second-line setting that the phase 3 trial of HRS-8080 targets, and as yet there's no indication that patient enrolment will be enriched for ESR1-mutated disease. Most western SERD players now see first-line combinations with CDK4/6 inhibition as a more fruitful avenue, and AstraZeneca has recently played up camizestrant's promise in a setting between the first and true second line. It's notable that Astra has effectively given up on second-line camizestrant.

Advanced-stage SERDs in ER+ve HER2-ve breast cancer

Notes: AI=aromatase inhibitor; *technically a “protac” degrader; **said to be a CERAN/SERD. Source: OncologyPipeline.