According to results from a phase 1 trial, the first-in-class KIT6 inhibitor PF-07248144 plus fulvestrant demonstrated durable response and tolerable safety among patients with ER-positive, HER2-negative metastatic breast cancer who had progressed on or after CDK4/6 inhibition and endocrine therapy.

These data were first presented by Toru Mukohara, MD, National Cancer Center East, Kashiwa, Japan and coauthors, at the 2025 Miami Breast Cancer Conference.

This phase 1 dose expansion trial enrolled patients with ER-positive, HER2-negative metastatic breast cancer, castration-resistant prostate cancer, and non-small cell lung cancer, who received the KIT6 inhibitor as monotherapy. Patients with ER-positive, HER2-negative metastatic breast cancer in the second line or later who had progressed on or after CDK4/6 inhibition and endocrine therapy were included in the dose expansion portion evaluating the KIT6 inhibitor plus fulvestrant. The recommended dose for expansion was determined to be 5 mg PF-07248144 along or in combination with 500 mg fulvestrant. The end points for this study included safety and antitumor activity.

Among evaluable patients treated with the KIT6 inhibitor and fulvestrant (n = 43), there was an objective response rate of 37.2% and a clinical benefit rate of 55.8%. The median duration of response was not reached (95% confidence interval, 7.2 months to not evaluable), and the median progression-free survival was 10.7 months. The study authors noted that the antitumor activity was consistent across all subgroups, regardless of biomarker mutation status, endocrine and CDK4/6 inhibitor sensitivity status, and line of therapy.

In the combination cohort, there were 62.8% of patients who experienced a grade ≥3 treatment-related adverse event. The most common treatment related adverse events in this cohort included dysgeusia, neutropenia, anemia, leukopenia, thrombocytopenia, increased AST levels, and fatigue. There were not grade 5 treatment-related adverse events reported.

Study authors concluded that these results suggest “PF-07248144 may overcome endocrine and CDK4/6 inhibitor resistance, and provide a novel mechanism of action to address high, unmet medical need in hormone receptor-positive metastatic breast cancer” in this treatment setting.

Source:

Ryan C. PF-07248144 plus fulvestrant is safe, active in pretreated ER+/HER2– metastatic breast cancer. OncLive. Published on March 7, 2025. Accessed March 10, 2025. https://www.onclive.com/view/pf-07248144-plus-fulvestrant-is-safe-active-in-pretreated-er-her2-metastatic-breast-cancer