Puxitatug samrotecan (AZD8205) vs chemotherapy in patients with B7-H4–selected advanced/metastatic endometrial cancer: The phase 3 randomized Bluestar-Endometrial01 (BE01)/GOG-3110/ENGOT-EN28 trial.

Abstract

TPS5647 Background: The transmembrane glycoprotein B7-H4 is highly expressed in endometrial cancer (EC), with limited expression in normal tissue; therefore, B7-H4 is an attractive antibody–drug conjugate (ADC) target in the treatment of advanced/recurrent EC. Puxitatug samrotecan (Puxi-Sam), a novel B7-H4-directed topoisomerase I inhibitor ADC, was assessed as monotherapy in the first-in-human, Phase 1/2a BLUESTAR trial in several B7-H4-expressing tumors, and showed manageable toxicity and promising efficacy during dose escalation in heavily pre-treated patients (pts). 1 In pts with advanced/recurrent EC, who progressed after available standard of care therapy (including chemotherapy and/or a programmed death [PD]-ligand [L] 1 inhibitor), objective response rates (ORRs) were 34.6% and 38.5% with 2.0 and 2.4 mg/kg Puxi-Sam, respectively, after ≥13 weeks of follow-up. 2 The safety profile of Puxi-Sam was favorable, with manageable hematologic and gastrointestinal toxicities, no adverse events (AEs) leading to discontinuation, and low dose reduction rates due to treatment-related AEs. 2 Following these encouraging results, Bluestar Endometrial01, a global Phase 3 trial, will investigate Puxi-Sam monotherapy versus physician’s choice of chemotherapy in pts with B7-H4-selected EC whose disease has progressed following prior platinum-based chemotherapy and immunotherapy. Methods: This Phase 3, randomized, open-label, multicenter study includes pts with B7-H4-selected advanced/metastatic EC that progressed following platinum-based chemotherapy and anti-PD-1/anti-PD-L1 therapy. Approximately 700 pts will be randomized 1:1 to either Arm A: Puxi-Sam (2.4 mg/kg; intravenous [IV] on Day 1 every 3 weeks [q3w]) or Arm B: either doxorubicin (60 mg/m 2 IV on Day 1 q3w) or paclitaxel (80 mg/m 2 IV on Days 1, 8, and 15 in 28-day cycles). The primary outcomes are progression-free survival (PFS) and overall survival (OS). Secondary outcomes include ORR, duration of response (DoR), second PFS, time until first subsequent anticancer therapy (TFST) and second subsequent anticancer therapy (TSST) after discontinuation of the randomized treatment, or death, and time until discontinuation of treatment (TDT) for any reason, or death. All outcomes are to be assessed for Arm A versus Arm B. Safety will be assessed throughout. Clinical trial information: NCT07044336. First Patient In date: Aug 1, 2025. 1. Meric-Bernstam F, et al. Ann Oncol. 2024;35:S485–S486. 2. Gaillard S, et al. Gynecol Oncol. 2025;200:347–348. Editorial acknowledgment: Medical writing assistance was provided by Lewis C Rodgers, PhD, of Omnicom Health Medical Communications, and was funded by AstraZeneca. Clinical trial information: NCT07044336 .