The Phase 1/2a BLUESTAR trial showed promising results for puxitatug samrotecan (Puxi-Sam), a B7-H4-targeting antibody-drug conjugate developed for advanced gynecologic cancers. The drug delivers a topoisomerase 1 inhibitor directly to tumor cells expressing B7-H4, a protein commonly found in endometrial and ovarian cancers.
At the recommended 2.4 mg/kg dose, Puxi-Sam achieved an objective response rate of 47.1% and a median progression-free survival of 7.2 months in patients with advanced endometrial cancer. Among patients previously treated with both platinum chemotherapy and immunotherapy, the response rate reached 60.6%, helping support the drug’s FDA Breakthrough Therapy Designation. In platinum-resistant ovarian cancer, the response rate was 24.4% with a median progression-free survival of 5.7 months.
Responses were observed across different tumor subtypes and B7-H4 expression levels. The most common side effects included nausea, neutropenia, and anemia, which were generally manageable. Treatment discontinuation rates were low, and severe pneumonitis was rare.
Based on these findings, the global Phase 3 BLUESTAR-Endometrial-01 trial is now comparing Puxi-Sam with standard chemotherapy in patients with advanced endometrial cancer who have progressed after platinum-based therapy and immunotherapy.