Abstract PS5-03-03: Trop2-directed antibody-drug conjugate shr-a1921 combined with pd-l1 inhibitor adebrelimab for patients with advanced triple negative breast cancer: results from a phase 2, multi-cohort, open-label, non-controlled trial

Abstract Background: The advent of novel antibody-drug conjugates (ADCs) has greatly changed the treatment landscape of advanced HER2-negative breast cancer. Preclinical studies have showed potential synergistic effect between ADCs and immunotherapies, while the clinical evidence remains limited. Our phase 2, multi-cohort, open-label, non-controlled trial (NCT06433609), was designed to evaluate the efficacy and safety of ADCs with distinct targets combined with PD-L1 inhibitor adebrelimab in pts with pretreated advanced HER2-negative breast cancer. Here, we present the preliminary results of TROP2-ADC SHR-A1921 combined with adebrelimab in pts with advanced triple negative breast cancer (TNBC). Methods: Pts with HER2-negative advanced breast cancer who had experienced disease recurrence or progression on or after at least one line of systematic therapy were eligible for this trial. Prior PD-1/L1 inhibitors were allowed. Eligible pts with advanced TNBC enrolled in Cohort 2 received SHR-A1921 (3 mg/kg IV on day 1, Q3W) and adebrelimab (1200mg IV on day 1, Q3W). The primary endpoint was objective response rate (ORR) per investigator based on RECIST v1.1. Secondary endpoints included disease control rate (DCR), clinical benefit rate (CBR), duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Results: Between Sept. 6th, 2024 and Dec. 31st, 2024, 15 pts were enrolled in Cohort 2. The median age was 52 years (range, 29-70), and pts had the median one (range, 0-8) prior treatment at the advanced setting. Eleven pts (73.3%) had ECOG PS of 1, eight (53.3%) were PD-L1-positive (CPS≥1) and 13 (86.7%) had visceral metastases, with 8 (53.3%) having ≥3 metastatic sites. With a median follow-up of 5.5 mo (range, 1.2-8.9), all of pts had at least one efficacy assessment. The confirmed ORR was 46.7% (95% confidence interval [CI], 21.2-73.4) with a median DoR of 4.6 mo. CBR was 46.7% (95%CI, 21.2-73.4), and DCR was 86.7% (95%CI, 59.5-98.3). Of note, among 6 pts with PD-L1-negative diseases, 2 pts achieved PR and 1 pt achieved PR to be confirmed. Nine PFS events were observed, and the median PFS was 5.1 mo (95%CI 3.1-NA). Two pts died after disease progression, and the median OS was unmatured. Treatment-related adverse events (TRAEs) occurred in all pts, and mostly were of grade 1-2. Grade≥3 TRAEs occurred in 2 pts (13.3%), including one (6.7%) grade 3 stomatitis and one (6.7%) grade 3 lymphocyte decreased. Eight pts experienced dose reduction of SHR-A1921 due to TRAEs. No dose discontinuation and no death due to AE was reported. Conclusion: The combination of SHR-A1921 and adebrelimab demonstrated promising anti-tumor efficacy and manageable safety in pretreated TNBC pts regardless of PD-L1 status, warranting further investigations in this population. Our exploration of ADCs combined with adebrelimab in HER2-negative advanced breast cancer is still ongoing. Citation Format: T. Wang, W. Zhao, J. Xiao, J. Zhou, X. Shi, Q. Li, Z. Jiang. Trop2-directed antibody-drug conjugate shr-a1921 combined with pd-l1 inhibitor adebrelimab for patients with advanced triple negative breast cancer: results from a phase 2, multi-cohort, open-label, non-controlled trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-03-03.