B7-H4-directed antibody-drug conjugate puxitatug samrotecan (AZD8205) delivered a 47.1% confirmed objective response rate in B7-H4-expressing recurrent or progressive endometrial cancer in the BLUESTAR Phase 1/2a trial, according to data presented at ASCO. At the 2.4 mg/kg dose, the program reported an 84.3% 12-week disease control rate, median duration of response of 7.1 months, and median progression-free survival of 7.2 months. In an analysis of heavily pretreated patients who had received both prior platinum-based chemotherapy and prior anti-PD-1/PD-L1 therapy, the confirmed ORR climbed to 60.6% with median PFS of 7.1 months. The company stated the efficacy supported FDA Breakthrough Therapy Designation in this endometrial population after prior platinum and immunotherapy. The ADC also showed activity in ovarian cancer in the same dose cohort, with a 24.4% confirmed ORR reported in a heavily pretreated platinum-resistant subgroup. The trial’s biomarker strategy emphasizes B7-H4 expression, designed to focus on tumor-associated target presentation while limiting expression in normal tissue.