Pfizer Launches Phase III Trial of KAT6 Inhibitor PF-07248144 Combined with Fulvestrant for HR+/HER2- Breast Cancer

▎Armstrong

On July 14, 2025, Pfizer registered a Phase III clinical trial on Clinicaltrials.gov for the KAT6 inhibitor PF-07248144 in combination with fulvestrant for the treatment of HR+/HER2- breast cancer.

This Phase III clinical trial plans to enroll 400 patients with advanced HR+/HER2- breast cancer and is expected to be preliminarily completed by 2027.

In May this year, Pfizer announced the latest Phase I clinical data of PF-07248144 in treating ER+/HER2- metastatic breast cancer at the ASCO meeting. The recommended dose expansion cohort (RDE) enrolled a total of 107 patients. All patients had been treated with CDK4/6 inhibitors and ER inhibitors. Thirty-five patients received 5mg PF-07248144 monotherapy, 43 patients received 5mg PF-07248144 plus fulvestrant combination therapy, and 29 patients received 1mg PF-07248144 plus fulvestrant combination therapy.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 reactions 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 reaction is reversible and can be controlled by dose adjustment. No pneumonia-related adverse reactions occurred.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 for an upfront payment of $12 million, with the total deal amount exceeding $500 million. Qilu Pharmaceutical and Kangchen Pharmaceutical’s KAT6 inhibitors have entered clinical stages. At this year’s AACR conference, Qilu Pharmaceutical's QLS1034, Renfu Pharmaceutical's HW321005, Henlius’ HLX97, and Yingchuang Medicine's KAT6 inhibitor all reported preclinical data.