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

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 [¹⁴C] 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.