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.

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.