SHR-A2102 in combination with adebrelimab as first-line treatment in patients with locally advanced or metastatic squamous or non-squamous non-small cell lung cancer (NSCLC): Results from a phase 1b/2 study.

Abstract

8527 Background: SHR-A2102 is a novel antibody-drug conjugate composed of a monoclonal antibody targeting nectin-4, a cleavable linker, and a topoisomerase I inhibitor payload. Here, we report the preliminary efficacy and safety of SHR-A2102 plus adebrelimab (an anti-PD-L1 antibody) as first-line therapy in patients with locally advanced or metastatic squamous or non-squamous NSCLC. Methods: This is a multicenter, open-label phase 1b/2 study (NCT06512051). In the phase 2 part, patients aged 18-70 years with ECOG PS 0-1 and histologically/cytologically confirmed stage IIIB-IV squamous (cohort A) or non-squamous (cohort B) NSCLC who had received no prior systemic therapy were enrolled. All patients received intravenous SHR-A2102 (8 mg/kg, day 1 Q3W) plus adebrelimab (1200 mg, day 1 Q3W) until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR). Results: Between Dec 13, 2024 and Nov 19, 2025, 67 patients were enrolled and received treatment (27 with squamous NSCLC and 40 with non-squamous NSCLC). In cohort A, 92.6% were male, the median age was 64 years (range 42-70), 14 patients had PD-L1 TPS 1-49%, and 13 patients had PD-L1 TPS ≥50%. In cohort B, 60.0% were male, the median age was 62 years (range 42-70), 7 patients had PD-L1 TPS <1%, 20 patients had PD-L1 TPS 1-49%, and 13 patients had PD-L1 TPS ≥50%. Efficacy was evaluated in 26 and 33 patients from cohorts A and B, respectively, while all patients were included in the safety analysis. As of Nov 30, 2025, the median follow-up was 9.1 months (range 2.0-11.1), with 9.9 months (range 3.0-11.0) with squamous NSCLC and 9.0 months (range 2.0-11.1) with non-squamous NSCLC. Antitumor activities are shown in Table 1. In patients with PD-L1 TPS ≥1%, ORR was 80.8% (95% CI 60.6%-93.4%) for squamous NSCLC and 69.2% (95% CI 48.2%-85.7%) for non-squamous NSCLC. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 53.7% (36/67) of patients. The most common Grade ≥3 TRAEs were decreased neutrophil count (32.8%), decreased white blood cell count (14.9%), and anemia (9.0%). Conclusions: These results suggested the combination of SHR-A2102 and adebrelimab as the first-line therapy is a promising treatment strategy in patients with squamous or non-squamous NSCLC, supporting further investigation. Clinical trial information: NCT06512051 . Efficacy summary. Squamous NSCLC (N=26) Non-squamous NSCLC (N=33) Total (N=59) ORR, % (95% CI) 80.8 (60.6-93.4) 69.7 (51.3-84.4) 74.6 (61.6-85.0) DCR, % (95% CI) 96.2 (80.4-99.9) 97.0 (84.2-99.9) 96.6 (88.3-99.6) DoR (months), median (95% CI) NR (4.4-NR) NR (5.7-NR) NR (6.5-NR) 6-month PFS rates, % (95% CI) 64.1 (42.3-79.5) 78.9 (58.9-90.0) 71.8 (57.6-81.9)