Updated safety and efficacy of puxitatug samrotecan (Puxi-Sam, AZD8205) in patients (pts) with endometrial cancer (EC) or ovarian cancer (OC): Phase 1/2a BLUESTAR study.
Year: 2026
Type: conference-abstract
Abstract: 5515 Background: B7-H4, a transmembrane glycoprotein that negatively regulates T cells, is highly expressed in EC and OC. Puxi-Sam (AZD8205), a B7-H4–directed topoisomerase I inhibitor antibody–drug conjugate, showed manageable toxicity and promising antitumor activity in BLUESTAR (NCT05123482) dose-escalation. Here, we report updated safety and efficacy results as EC and OC expansion cohorts are fully enrolled. Methods: Eligible pts were ≥18 years old with relapsed/metastatic B7-H4–positive (≥25% tumor cell staining by central immunohistochemistry) EC or OC and an ECOG PS ≤1. Pts had progressed on prior standard-of-care therapy including platinum-based chemotherapy. Pts with EC received Puxi-Sam at 2.0 or 2.4 mg/kg IV Q3W and pts with OC received Puxi-Sam at 1.6 or 2.4 mg/kg IV Q3W. The primary objectives were to assess safety and tolerability; secondary objectives included assessment of antitumor activity per RECIST 1.1. Results: As of October 30, 2025, 93 pts with EC received Puxi-Sam at 2.0/2.4 mg/kg and 78 with OC at 1.6/2.4 mg/kg. Pts with EC had a median age (min–max) of 63.5 (52–78)/65 (34–81) years, respectively, and median prior lines of therapy (LOT) was 1. Pts with OC had a median age of 58 (28–79)/59 (35–74) years, respectively, and median prior LOT was 2. Treatment-related adverse events (TRAE) occurred in 92.9%/88.2% of pts with EC (2.0/2.4 mg/kg); 42.9%/47.1% had Grade ≥3 TRAEs, most commonly neutropenia (23.8%/31.4%) and anemia (16.7%/27.5%). TRAEs occurred in 87.9%/97.8% of pts with OC (1.6/2.4 mg/kg); 30.3%/75.6% had Grade ≥3 TRAEs, most commonly neutropenia (24.2%/60.0%) and anemia (9.1%/37.8%). One pt (1.1%) with EC and 5 (6.4%) with OC discontinued treatment due to TRAEs. Antitumor activity of Puxi-Sam was most notable in EC at 2.4 mg/kg, with an objective response rate (ORR) of 48% and durable response of 7.1 months; at 2.0 mg/kg in EC, ORR was 34.1%. In OC, ORR was 12.1% at 1.6 mg/kg and 24.4% at 2.4 mg/kg (Table). Conclusions: Puxi-Sam showed a favorable safety profile and robust antitumor efficacy, supporting continued development, and is now being investigated in the Phase 3 BLUESTAR-Endometrial01 (NCT07044336) study. Clinical trial information: NCT05123482 . Efficacy (interim response evaluable pts). EC 2.0 mg/kgn=41 EC 2.4 mg/kgn=50 OC 1.6 mg/kgn=33 OC 2.4 mg/kgn=45 ORR, % (95% CI) 34.1 (20.1–50.6) 48.0 (33.7–62.6) 12.1 (3.4–28.2)* 24.4 (12.9–39.5) Complete response, n 1 1 0 0 Partial response, n 13 23 4 11 Stable disease, n 17 21 22 26 Progressive disease, n 10 5 5 8 Median duration of response, months (95% CI) 6.2 (5.5–NE) 7.1 (4.5–NE) 5.8 (2.8–NE) 7.0 (4.0–NE) Disease control rate at 12 weeks, % (95% CI) 70.7(54.5–83.9) 86.0(73.3–94.2) 54.5(36.4–71.9) 64.4(48.8–78.1) Median progression-free survival, months (95% CI) ‡ 7.0(4.5–9.0) § 8.1(6.8–9.2) ¶ 4.8(2.8–5.8) 5.7(4.1–9.5) *2 pts were non-evaluable. ‡ Full analysis set. § n=42. ¶ n=51. NE, not estimable.
Source: Journal of Clinical Oncology
Authors: Linda R. Mileshkin, Stephanie Gaillard, Robin Guo, Yoichi Naito, Karen Finkelstein, Anna Tinker, Wendel Naumann, Gun Min Kim, Toon Van Gorp, Marloes Van Dongen, Thatthan Suksombooncharoen, Tatsunori Shimoi, Jing Wang, Joo Ern Ang, Theresa Proia, Sarah Cross, Chris Gibbs, Mohamed Zaid, Andreea Varga, Funda Meric-Bernstam
Institutions: Peter MacCallum Cancer Centre, Johns Hopkins University, Memorial Sloan Kettering Cancer Center, National Cancer Center Hospital East, BC Cancer Agency, Levine Cancer Institute, Yonsei University, KU Leuven, The Netherlands Cancer Institute, Chiang Mai University, National Cancer Center Hospital, Central South University, Hunan Cancer Hospital, Cancer Research UK Cambridge Center, AstraZeneca (United States), AstraZeneca (United Kingdom), The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7162494880