Background and Objective <p>Vepdegestrant is a selective, oral PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader in development for the treatment of ER-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. The current study was conducted to estimate the relative bioavailability of single 200-mg doses of commercially representative vepdegestrant tablets (2 × 100-mg strength and 1 × 200-mg strength) compared with a single 200-mg dose of the pivotal phase 3 vepdegestrant tablets (2 × 100-mg strength).</p> Methods <p>This phase 1, randomized, open-label, three-period, three-treatment, six-sequence, crossover, single-dose study in healthy adults was conducted according to bioequivalence standards. Participants were to receive three vepdegestrant treatments over three treatment periods. Serial pharmacokinetic blood samples were collected up to 168 h after vepdegestrant administration in each period.</p> Results <p>Fifty-two participants were enrolled and treated in the study. Following administration, vepdegestrant plasma concentration–time curves for both commercially representative tablets (test) and the pivotal phase 3 tablets (reference) were nearly superimposable. The 90% confidence intervals for the test/reference adjusted geometric means ratios of vepdegestrant area under the plasma concentration–time curve from time zero to infinity and maximum plasma concentration for both commercially representative tablets relative to the pivotal phase 3 tablets fell completely within prespecified standard bioequivalence limits (80.00–125.00%). Adverse event rates were similar across tablet formulations.</p> Conclusions <p>Commercially representative vepdegestrant tablets demonstrated bioequivalence with the pivotal phase 3 vepdegestrant tablets; all tablet formulations of vepdegestrant 200 mg were well tolerated.</p> Clinical Trial Registration <p>NCT06347861; registered March 29, 2024.</p>