SHR-A1811 plus adebrelimab in unresectable or metastatic triple-negative breast cancer: Results from a phase 1b/2 expansion cohort.

1103 Background: SHR-A1811 is a novel HER2-directed antibody-drug conjugate with promising antitumor activity in breast cancer (BC), yielding a confirmed objective response rate (ORR) of 79.4% in HER2 positive BC, 60.9% in HER2 low-expressing BC, and 52.0% in triple-negative BC (TNBC) as monotherapy. We evaluated SHR-A1811 in combination with adebrelimab (anti-PD-L1 antibody), pyrotinib (irreversible, pan-HER receptor tyrosine kinase inhibitor), pertuzumab, or albumin-bound paclitaxel in unresectable or metastatic breast cancer in an open-label, dose-finding and efficacy expansion phase 1b/2 study. Here, we report the safety and efficacy results of the SHR-A1811 plus adebrelimab cohort. Methods: Patients (pts) with unresectable or metastatic TNBC and ≥1 line of prior treatment received intravenous SHR-A1811 at an escalating dose of 4.8 mg/kg and 5.6 mg/kg Q3W, in combination with adebrelimab (1200 mg Q3W) in phase 1b part. In phase 2 part, TNBC pts with no systematic antitumor therapy in the recurrent or metastatic setting were treated with SHR-A1811 at 4.8 mg/kg Q3W plus adebrelimab. Primary endpoints were safety and ORR. The data cutoff date was Nov 30, 2024. Results: Fifty TNBC pts were enrolled in total. In phase 1b, 8 pts were enrolled and treated. No DLT was observed. The confirmed ORR was 66.7% (2/3) and 60.0% (3/5) in the 4.8 mg/kg and 5.6 mg/kg dose group, respectively. In phase 2, 42 treatment naive TNBC pts were enrolled. 13 (31.0%) pts had ≥3 metastases sites, 22 (52.4%) pts were HER2-low (IHC 2+/ISH- or IHC 1+)/ultra-low (IHC 0-1), 20 (47.6%) pts were HER2-nul (IHC 0), and 30 (71.4%) pts were PD-L1-positive (CPS ≥1). At the time of data cutoff, the median follow-up time was 4.6 mo (range, 0.2-10.4). Among efficacy evaluable TNBC pts, the overall ORR was 66.7% (26/39) (Table). ORR was 77.8% (21/27) in the PD-L1-positive subgroup. The 6-month PFS rate was 86.2%. SHR-A1811 plus adebrelimab was well tolerated with no new safety concerns identified. Treatment-emergent adverse events of grade ≥3 occurred in 26 (61.9%) out of 42 pts in phase 2, with decreased neutrophil count (45.2%), decreased white blood cell count (33.3%), and decreased lymphocyte count (9.5%) being the most common. Conclusions: SHR-A1811 plus adebrelimab had a good safety and tolerability profile. The combination showed encouraging antitumor activity in unresectable or metastatic TNBC, irrespective of HER2 or PD-L1 expression status. Clinical trial information: NCT05353361 . Phase 2 preliminary efficacy summary 1 . SHR-A1811 4.8 mg/kg + adebrelimab CPS ≥1 (N = 30) CPS <1 (N = 12) Total (N = 42) ORR, Overall 2 21/27 (77.8) 5/12 (41.7) 26/39 (66.7) HER2-low/-ultralow 11/13 (84.6) 4/9 (44.4) 15/22 (68.2) HER2-nul 10/14 (71.4) 1/3 (33.3) 11/17 (64.7) 6-mo PFS rate, % (95% CI) 88.9 (43.3, 98.4) 78.8 (38.1, 94.3) 86.2 (60.7, 95.7) 1 HER2 and PD-L1 results were based on central lab assessment. 2 Data are n/N1(%) with N1 = the number of efficacy evaluable patients.