ARTEMIS-003: A phase 2 study of HS-20093 (GSK5764227) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

150 Background: B7 homolog 3 protein (B7-H3) is a promising therapeutic target in solid tumors including prostate cancer. This multicenter, open label, phase 2 study aimed to evaluate the efficacy and safety of HS-20093 (GSK5764227), a novel B7-H3 targeted antibody–drug conjugate (ADC) with topoisomerase 1 inhibitor payload, in patients (pts) with mCRPC (registration number: NCT06001255). Methods: Pts who had progressed after at least first-line standard therapy were enrolled and received HS-20093 8.0 mg/kg every 3 weeks intravenously. The primary endpoint was confirmed objective response rate (cORR) as assessed per RECIST 1.1 and PCWG3 criteria in pts with target lesion at baseline. Safety and other efficacy endpoints were analyzed in pts who received ≥1 dose of HS-20093. Results: As of July 20th, 2025, a total of 50 Chinese adult pts were enrolled and all received ≥1 dose of HS-20093. The median follow-up time was 8.7 (range: 0.1, 16.7) months. Median age was 68 (range: 49, 79) years old and 72.0% of the pts had ECOG PS 1. All pts had been pretreated with novel hormonal therapy and 72.0% had received prior taxane-based chemotherapy. The median number of prior therapies was 2 (range:1, 8). Of 33 pts with target lesion, the cORR was 33.3% (95% CI: 18.0, 51.8) and disease control rate was 87.9% (95% CI: 71.8, 96.6). The median duration of response was not reached. A total of 16 pts showed at least 50% decrease on prostate specific antigen (PSA 50 ), with a confirmed PSA 50 response rate of 32.0%. The median radiological progression free survival (rPFS) was not reached and the rate of rPFS at 9 months was 55.7% (95% CI: 34.3, 72.5). HS-20093 showed anti-tumor activity in both taxane-naïve and taxane-treated pts (Table 1). Treatment-related adverse events (TRAEs) were observed in 49 patients (98.0%), of which 54.0% were Grade ≥3 and 20.0% were serious adverse events. The most frequent TRAEs were hematologic toxicity and gastrointestinal toxicity, in line with previously reported safety profile. One Grade 2 interstitial lung disease event occurred. Conclusions: HS-20093 monotherapy showed encouraging anti-tumor activity and was generally well-tolerated with a manageable safety profile in pts with mCRPC. Clinical trial information: NCT06001255 . Efficacy. Population TotalN=50 Taxane-naïve in mCRPC settingN=22 Taxane-treated in mCRPC setting N=28 cORRn (%) (95% CI) N*=3311 (33.3) (18.0, 51.8) N*=134 (30.8) (9.1, 61.4) N*=207 (35.0) (15.4, 59.2) cPSA 50 n (%) (95% CI) 16 (32.0) (19.5, 46.7) 5 (22.7) (7.8, 45.4) 11 (39.3) (21.5, 59.4) 9-month rPFS rate% (95% CI) 55.7 (34.3, 72.5) 62.9 (26.4, 85.1) 50.3 (24.1, 71.7) *Patients had target lesion at baseline. c, confirmed; CI, confidence interval; PSA 50 , at least 50% decrease on prostate specific antigen; rPFS, radiological progression free survival.