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 cancerSERDCompany2nd-line studyOrserduMenariniUS approved in ESR1m disease, based on Emerald trial: PFS HR=0.55 vs Faslodex or AI; OS not significantImlunestrantLillyAwaiting US approval: Ember-3 showed PFS benefit vs Faslodex or AI only in ESR1m diseaseVepdegestrant*Pfizer/ ArvinasFiled for US approval: Veritac-2 showed PFS benefit vs Faslodex only in ESR1m diseasePalazestrant**OlemaOpera-01, vs Faslodex or AI, PFS primary endpointHRS-8080Jiangsu HengRuiPh3 just started, vs Faslodex or AI, PFS primary endpointGiredestrantRocheFailed ph2 Acelera trial, focus now on 1st-line useCamizestrantAstraZenecaPositive data from ph2 Serena-2 trial, but focus now on earlier-line useAmcenestrantSanofiDiscontinued after failing ph2 Ameera-3 trialNotes: AI=aromatase inhibitor; *technically a “protac” degrader; **said to be a CERAN/SERD. Source: OncologyPipeline.
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
