Neoadjuvant almonertinib followed by chemo-immunotherapy in II-IIIb EGFR-mutant NSCLC: A single arm, phase II study (NEOVADE).

Abstract

8509 Background: Neoadjuvant target therapy has improved objective response rate (ORR) or major pathological response (MPR) of stage IIA-IIIB non-small cell lung cancer (NSCLC) with EGFR mutation. EGFR-TKI-induced evolution indicated a hot-tumor status in residual disease. However, the role of immunotherapy in this phrase remained unclear. Here, we present the results of a phase II, open-label study investigating the efficacy and safety of sequential almonertinib and chemo-immunotherapy (IO) in potentially resectable stage IIA-IIIB EGFR-mutant NSCLC patients. (NCT06300424). Methods: Untreated patients with II-IIIB NSCLC were enrolled in this study. Patients received almonertinib for 6 weeks, followed by 3 cycles of adebrelimab and chemotherapy before surgery. Primary end point was MPR, Secondary end points included pathological complete response (PCR), ORR, event-free survival (EFS), overall survival (OS) and safety. Results: A total of 32 patients were enrolled from Apr 2024 to Aug 2025. EGFR mutation subtype was 19del in 16 (50.0%) patients, L858R in 11 (34.4%) patients, others in 5 (15.6%) patients. All the patients completed neoadjuvant almonertinib, 30 (93.8%) patients completed 3 circles of chemo-IO and underwent surgery, R0 was achieved in 29 (96.7%) patients. ORR was 46.9% (15/32) and 59.4% (19/32) after target therapy and chemo-IO, respectively. MPR was documented in 13 (40.6%) patients, including PCR in 5 (15.6%) patients. In patients underwent resection, MRP and PCR rate were 66.7% and 33.3% in patients with PD-L1≥1%, compared with 21.4% and 0% in PD-L1 ＜1% subgroup, respectively, N downstage was confirmed in 44.8% (13/29) patients. After a median follow-up of 13.5 months (interquartile range [IQR], 7.5–16.1 months), 31 (96.9%) patients were alive. Median EFS and OS were not reached. One-year EFS and OS rate was 89.5% and 95.2%, respectively. Grade ≥ 3 AEs occurred in 28 (87.5%) patients during neoadjuvant therapy. Conclusions: This study met its primary endpoint, indicating almonertinib followed by chemo-IO was a feasible neoadjuvant treatment in patients with resectable stage IIA-IIIB EGFR-mutant NSCLC, especially in patients with PD-L1 expression. The study was partially supported by Jiangsu Hengrui Pharmaceuticals and Hansoh Pharmaceutical Group Co. Ltd. Clinical trial information: NCT06300424 . Primary and secondary outcomes. Outcomes ITT (N=32) Resection (N=29) Major pathological response rate 40.6% (13/32) 44.8% (13/29) PD-L1＜1% 18.8% (3/16) 21.4% (3/14) PD-L1≥1% 62.5% (10/16) 66.7% (10/15) Complete pathological response rate 15.6% (5/32) 17.2% (5/29) PD-L1＜1% 0.0% (0/16) 0.0% (0/14) PD-L1≥1% 31.3% (5/16) 33.3% (5/15) After receiving neoadjuvant TKI ORR 46.9% (15/32) 44.8% (13/29) DCR 93.8% (30/32) 96.6% (28/29) After receiving neoadjuvant TKI+IO ORR 59.4% (19/32) 58.6% (17/29) DCR 100.0% (32/32) 100.0% (29/29) TKI: Tyrosine kinase inhibitor; IO: Immunotherapy.