Abstract CT232: Efficacy and safety of toripalimab adjuvant therapy of high-risk factors in stage IA2-IB NSCLC without EGFR and ALK mutation after complete resection treatment (TORAT): A prospective, single-arm study

Abstract Background: There is a significant difference in survival among patients with stage I NSCLC (5-year OS: 68-92%), and the benefits of adjuvant chemotherapy in early NSCLC are limited. ADUARA study showed that in the IB subgroup of patients with EGFR mutations, postoperative use of osimertinib can reduce the risk of recurrence or death by 61%, ALINA shows that postoperative use of alectinib can reduce the risk of recurrence or death by 79% in IB patients with ALK mutations. However, there is no effective evidence of postoperative adjuvant therapy for early-stage patients (stage I) with negative driver genes currently. Patients with poor pathological subtypes such as micropapillary subtypes, solid components, and tumor spread through air spaces (STAS), especially those that account for a high proportion, of postoperative recurrence and metastasis are more likely to occur. At present, a series of PD-1/PD-L1 monoclonal antibody preparations represented by Toripalimab have shown promising application prospects in postoperative adjuvant therapy. The Impower010 study showed that immunotherapy extended DFS by more than 30 months (68.5 months VS 37.3 months, HR: 0.70) in postoperative adjuvant therapy for stage II-IIIa and PD-L1 ≥ 1% NSCLC, and safety is well. Keynote091 shows that pembrolizumab prolongs the DFS effect in postoperative adjuvant therapy (53.6 vs 42.0; HR 0.76). However, whether they can benefit from adjuvant treatment at an earlier stage (IA2-IB) is unknown. Methods: This is a prospective, open, single-center, single-arm phase II clinical study. 51 eligible patients (aged ≥18 years, WHO PS 0/1, completely lobectomy-resected Stage IA2-IB [AJCC 8th edition] EGFR and ALK mutation-negative who with high-risk factors including pathology confirmed solid and/or micropapillary component ≥10%, and/or Spread Through Air Space, and/or pleural invasion, and/or poorly differentiated) and tumor PD-L1 TPS>1% will be enrolled within 8 weeks to received Toripalimab 240 mg Q3W for up to 1 years(up to 16 times). Primary endpoint: 3-year DFS rate, secondary endpoints: DFS, overall survival(OS),3-year OS rate,5-year OS rate, and safety. Exploratory endpoints include the correlation between genomic changes (mutations, copy number changes (CNV), structural changes, etc.), gene expression profiles, and the efficacy of trastuzumab in pre-treatment lesions and peripheral blood, tumor recurrence and peripheral blood during treatment, and the recurrence mechanism of trastuzumab in early NSCLC. 8 of planned 51 patients have been enrolled by December 31, 2024. Citation Format: Wei Wei, Zhenfa Zhang, Changli Wang, Dongsheng Yue. Efficacy and safety of toripalimab adjuvant therapy of high-risk factors in stage IA2-IB NSCLC without EGFR and ALK mutation after complete resection treatment (TORAT): A prospective, single-arm study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT232.