Puxitatug samrotecan (AZD8205) produced high response rates in B7-H4-expressing recurrent or progressive endometrial cancer in the Phase 1/2a BLUESTAR study, supporting an FDA Breakthrough Therapy Designation. In the endometrial cohort at the 2.4 mg/kg dose, the ADC delivered a 47.1% confirmed objective response rate and a median progression-free survival of 7.2 months. In a subgroup of 51 patients previously treated with platinum chemotherapy and prior anti–PD-1/PD-L1 therapy, the confirmed ORR increased to 60.6%, with a median PFS of 7.1 months. The ADC was also associated with activity in heavily pretreated ovarian cancer, with a 24.4% confirmed ORR at the same dose. BLUESTAR’s results position puxitatug samrotecan as a B7-H4-directed antibody-drug conjugate using a topoisomerase 1 inhibitor payload, with B7-H4 described as highly expressed in ovarian and endometrial tumors relative to normal tissue.