Extended Data Fig. 2: Pharmacokinetics and pharmacodynamics of PF-0728144 and tumor size change from baseline over time.
From: Inhibition of lysine acetyltransferase KAT6 in ER+HER2− metastatic breast cancer: a phase 1 trial
(a) Steady-state (C1D15) concentration-time profiles are provided as mean + standard deviation for each cohort. (b) H3K23Ac PD biomarker modulation in PBMC by single and multiple doses of PF-07248144 in part 1A (monotherapy) and part 1B (in combination with fulvestrant). Data are presented as median ± interquartile range (IQR). (c) H3K23Ac PD biomarker modulation by PF-07248144 after 14 days of treatment in tumor. High, medium, and low intensity H3K23Ac staining positive tumor cells from the entire tissue were evaluated from semi-quantitative image analysis. Percentage of high and medium intensity positive tumor cells were used for tumor H3K23Ac PD changes. Insert representative tumor area images of the IHC staining at 20X for the baseline (SCN) and on-treatment (C1D15) samples from patient #3: brown stain indicates the presence of H3K23AC antigen, while the blue counterstain highlights cell nuclei. The scale bar is 50 µm. (d) The patient had ER + /HER2– mBC and PIK3CA H1047R mutation and achieved confirmed PR (−39.72%) after PF-07248144 8 mg QD monotherapy with the duration of response of 15.7 months. (Images courtesy of Dr Toru Mukohara). BC, breast cancer; C, cycle; CRPC, castration-resistant prostate cancer; D, day; ER, estrogen receptor; Fulv, fulvestrant; HER2, human epidermal growth factor receptor 2; IQR, interquartile range; mBC, advanced/metastatic breast cancer; NA, not applicable; NE, not evaluable; PD, progressive disease; PF-8144, PF-07248144; PMBC, peripheral blood mononuclear cell; PR; partial response; pre, predose; Pt, patient; QD, once a day; SCN, screening; SD, stable disease.
