Adebrelimab shows signals as a new Tx option for resectable NSCLC.Perioperative adebrelimab plus chemotherapy improves event-free survival (EFS) and major pathological response (MPR) in individuals with resectable stage II/III non-small cell lung cancer (NSCLC) in an interim analysis.
The 2-year EFS rate was significantly higher in the adebrelimab vs placebo group in both blinded independent central review (74.8 percent vs 55.5 percent; hazard ratio [HR], 0.52; one-sided p<0.0001) and investigator assessments (77.2 percent vs 58.5 percent; HR, 0.49).
Adebrelimab also outperformed placebo in MPR (53.8 percent vs 18.4 percent; one-sided p<0.001) and pathologic complete response (pCR; 31.1 percent vs 7.6 percent) per blinded independent pathologic review. [AACR 2026, abstract CT014]
The benefits in pathological and clinical outcomes with adebrelimab were consistent across all subgroups, including PD-L1 tumour proportion score (TPS) status, clinical stage, histology, and smoking status, noted Dr Yi-Long Wu from the Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou, China, at AACR 2026.
There was an early overall survival (OS) trend favouring adebrelimab over placebo (2-year OS rate 89.1 percent vs 80.6 percent; HR, 0.57).
Safety profile
There were similar rates of grade ≥3 treatment-related adverse events (TRAEs) between the experimental and the placebo groups (52.6 percent vs 53.6 percent), but there were more serious TRAEs (18.3 percent vs 15.6 percent) and TRAEs leading to dose discontinuation (8 percent vs 4.4 percent) with the former than the latter.
The most common grade ≥3 TRAEs associated with adebrelimab were haematologic events, such as neutrophil count decrease (38.2 percent), WBC count decrease (17.1 percent), and anaemia (5.2 percent).
The adebrelimab group also had higher incidences of any immune-mediated AE (imAE; 18.3 percent vs 9.2 percent), grade ≥3 imAEs (4.4 percent vs 1.6 percent), and any imAE leading to dose discontinuation (5.2 percent vs 0.8 percent) than the placebo group.
“[Nonetheless,] the safety profile was manageable and consistent with that of the individual agents,” Wu said.
ctDNA clearance
Participants with pre-surgery ctDNA clearance in the adebrelimab group were more likely to achieve MPR (positive predictive value [PPV] 83.1 percent vs 48.5 percent) and pCR (PPV 57.6 percent vs 21.2 percent) than those in the placebo group.
Pre-surgery ctDNA clearance was associated with improved EFS in both groups, with a trend toward longer EFS with adebrelimab vs placebo, regardless of clearance (cleared: HR, 0.85; not cleared: HR, 0.64).
Patients without ctDNA clearance at adjuvant cycle 1, day 1 had poor disease-free survival, with a trend favouring adebrelimab over placebo (HR, 0.25).
“ctDNA dynamics were predictive of pathological and clinical outcomes, providing a potential tool for refined perioperative risk stratification,” Wu said.
IgG4 anti-PD-L1 antibody
In the phase I part of this phase Ib/III study, perioperative adebrelimab, an IgG4 anti–PD-L1 antibody, showed promising efficacy and a favourable safety profile in resectable NSCLC when added to chemo. [J Thorac Oncol 2023;18:194-203; J Thorac Oncol 2025;20:S361]
In this phase III part of the trial, 501 patients (median age 60 years, 92 percent men) with untreated, resectable stage II/III (IIIA/T3N2M0 IIIB) NSCLC (per the American Joint Committee on Cancer v8) and without EGFR mutations/ALK alterations were randomized 1:1 to receive three cycles of adebrelimab 20 mg/kg or placebo with histology-based platinum-doublet chemo* Q3W, followed by surgery and 16 cycles of adjuvant adebrelimab 20 mg/kg or placebo Q3W.
Approximately three-quarters of participants were former smokers, 47 percent had stage IIIA disease, and 53 percent had PD-L1 TPS ≥1 percent. The most common histological type was squamous (79 percent). The median follow-up was 23.6 months.
“Our findings support perioperative adebrelimab + chemo as a new treatment option for resectable stage II/III NSCLC,” Wu concluded.