KAT6 marks another phase 1-to-3 push from Pfizer

With Pfizer's second-line breast cancer combo efforts leaning increasingly on the KAT6 inhibitor PF-07248144, in preference to the oral SERD vepdegestrant or CDK4 inhibitor atirmociclib, that effort has now gone into phase 3. A pivotal study of PF-07248144, first mentioned last year, is now live on clinicaltrials.gov, revealing that the KAT6 inhibitor is being combined with Faslodex and compared against investigator's choice in ER-positive HER2-negative breast cancer progressed after CDK4/6 inhibitor therapy. This trial will presumably test the 5mg that Pfizer earlier said was the go-forward PF-07248144 dose; the company had looked at 1mg but found that this didn't reduce dysgeusia, which along with neutropenia will be among adverse events to watch. The effort sees Pfizer moving aggressively from phase 1 straight into phase 3, just as it did with its EZH2 inhibitor mevrometostat. Its enthusiasm is driven by phase 1 data where PF-07248144 at 5mg plus Faslodex gave a 37% ORR, and Pfizer clearly wants to stay ahead of Olema's rival KAT6 inhibitor OP-3136. Other recent phase 1-to-3 progressions include AstraZeneca's puxitatug samrotecan and AZD0486, Bristol Myers Squibb's BMS-986365, and Revolution's daraxonrasib. KAT6 inhibitors in developmentProjectMechanismCompanyStatusPF-07248144KAT6 inhibitorPfizerPh3 +Faslodex, vs investigator’s choice, in post-CDK4/6i ER+ve HER2-ve breast cancerOP-3136KAT6A/B inhibitorOlema OncologyPh1 in solid tumoursMEN2312KAT6 inhibitorMenariniPh1 +/-Orserdu in post-CDK4/6i breast cancerBG-75202KAT6A/B inhibitorBeOnePh1 to start by YE 2025KC1086KAT6 inhibitorBeijing Konruns PharmaceuticalChinese IND granted in Jun 2025IDE251KAT6/7 inhibitorIdeaya BiosciencesUS IND filing planned in 2025HLX97-069KAT6A/B inhibitorShanghai Henlius (Fosun)IND filing planned in 2025HW321005KAT6A/6B inhibitorHumanwell HealthcarePreclinical poster at AACR 2025QLS1304KAT6A/B inhibitorQilu PharmaceuticalPreclinical poster at AACR 2025IST-477KAT6A inhibitorIsosterixPreclinical poster at AACR 2024UnnamedKAT6A degraderPrelude TherapeuticsLead selection planned in 2025UnnamedKAT6 inhibitorHangzhou InnogateDiscovery poster at AACR 2025Source: OncologyPipeline.