Pfizer's KAT6 Inhibitor PF-07248144 Demonstrates Promising Efficacy in ER+/HER2- Metastatic Breast Cancer, Pivotal Phase 3 Trial Underway

▎Armstrong

In May 2025, the latest Phase I clinical data of Pfizer's KAT6 inhibitor PF-07248144 for the treatment of ER+/HER2- metastatic breast cancer was published in the ASCO conference abstract. The recommended dose expansion cohort (RDE) enrolled a total of 107 patients. All patients had previously received CDK4/6 inhibitor and ER inhibitor therapies. Among them, 35 patients received 5mg PF-07248144 monotherapy, 43 patients received 5mg PF-07248144 combined with fulvestrant, and 29 patients received 1mg PF-07248144 combined with fulvestrant.The ORR of 1mg and 5mg PF-07248144 + fulvestrant treatment groups were 24.1% and 37.2%, respectively, the CBR were 37.9% and 55.8%, respectively, the mDOR were 4.6 months and 15.8 months, respectively, and the mPFS were 3.6 months and 10.7 months, respectively.In terms of safety, the most common grade 3 or higher adverse events were neutropenic anemia, with a grade 3 incidence rate of 20.7% and 39.5%, and a grade 4 incidence rate of 0% and 7%. This adverse event is reversible and can be managed through dose adjustment. No cases of pneumonia were reported.Pfizer is planning to launch a pivotal Phase III clinical trial.

In June last year, the Phase I clinical data of Pfizer's PF-07248144 was published in the journal Nature Medicine. The data presented at this ASCO meeting is an update from the same Phase I clinical trial.

Summary

In China, Insilico Medicine's KAT6 inhibitor ISM5043 was licensed to Menarini in January 2024, with an upfront payment of $12 million and a total deal value exceeding $500 million. KAT6 inhibitors from Qilu Pharmaceutical and Kangchen Pharmaceuticals have entered the clinical stage. At this year’s AACR conference, Qilu Pharmaceutical's QLS1034, Renfu Pharmaceutical's HW321005, Henlius Biotech's HLX97, and Yingchuang Medicine's KAT6 inhibitor all reported preclinical data.