Open‐Label Study Assessing Relative and Absolute Bioavailability of Oral Camizestrant Formulations and Food Effects in Healthy Postmenopausal Women

ABSTRACT Camizestrant is the next‐generation oral selective estrogen receptor degrader and complete estrogen receptor antagonist in Phase 3 development for hormone receptor‐positive breast cancer. To investigate the impact of manufacturing changes during pivotal Phase 3 studies, this open‐label, randomized crossover study of 32 postmenopausal healthy volunteers determined the relative bioavailability of a tablet used in early clinical studies (Phase 1 tablet), a tablet designed for late‐phase development (prototype Phase 3 tablet), and an oral solution. Absolute oral bioavailability in the fasted state (using a [ 14 C] camizestrant intravenous microtracer) and effects of a high‐fat meal on the prototype Phase 3 tablet were also determined. The geometric mean ratios (GMRs) of the prototype Phase 3/Phase 1 tablets (% [90% CI]) for C max and AUC, respectively were 98.7 (87.4–111.5) and 97.4 (92.6–102.5) at 75 mg ( n = 15), and 96.6 (86.9–107.5) and 100.4 (96.2–104.9) at 300 mg ( n = 15). GMRs of the prototype Phase 3 tablet/oral solution for C max and AUC were 96.2 (85.3–108.7) and 99.5 (94.6–104.6) at 75 mg ( n = 15). Fed‐to‐fasted C max and AUC GMRs were 106.2 (94.3–119.7) ( n = 16) and 109.8 (104.4–115.5) ( n = 15) at 75 mg ( n = 16), and 115.9 (104.3–128.7) and 102.3 (98.0–106.8) at 300 mg ( n = 15). Absolute oral bioavailability at 75 mg ( n = 6) and 300 mg ( n = 6) was 42.5% (36.8%–49.0%) and 55.1% (48.5%–62.5%). The formulations showed similar exposures, supporting the planned manufacturing changes. Camizestrant exhibited moderate bioavailability; exposures were similar under fasted and high‐fat meal conditions, supporting its administration with or without food.