Neoadjuvant Toripalimab Plus Chemotherapy for Resectable Stage II-IIIB Non-Squamous Non-Small Cell Lung Cancer with EGFR Mutations: A Multi-Center, Multi-Cohort, Exploratory Study.

TPS8120 Background: Neoadjuvant immunotherapy has been widely applied in the treatment of resectable stage II-IIIB NSCLC patients without driver gene mutation. However, as for the EGFR-positive patients, the therapeutic effect of neoadjuvant treatment, either TKI or chemotherapy, is far from satisfied and the outcome of neoadjuvant immunotherapy plus chemotherapy in these patients remains an unanswered but crucial question. Herein, we conducted a phase 2 prospective trial (NCT05962021). Methods: This is a multicenter, multi-cohort prospective phase 2 study in the treatment-naïve patients with resectable stage II-IIIB (N2) (AJCC 8th edition) non-squamous NSCLC harboring EGFR mutations (19DEL or L858R). Enrolled patients will be divided into two cohorts according to EGFR status and receive neoadjuvant toripalimab (240mg, q3w) plus platinum-based doublet chemotherapy (pemetrexed 500mg/m2 plus carboplatin AUC 5, q3w) for 3 cycles. Surgery will be performed after completion of neoadjuvant therapy based on the multidisciplinary discussion, while local radiotherapy will be considered if the patient cannot undergo surgery due to disease progression. Key inclusion criteria: non-squamous NSCLC, resectable stage II-IIIB (N2), EGFR mutations (19DEL or L858R), age≥18 years, ECOG PS 0-1 and adequate cardiopulmonary function. Exclusion criteria: prior systemic anticancer treatment, contraindication to immunotherapy, active autoimmune disease. Adequate pre-treatment tissue samples are required for RT-PCR or next-generation sequencing to determine the EGFR mutation status and PD-L1 expression immunohistochemical detection. The primary study endpoint is complete pathological response (pCR) rate, per blinded independent pathologist review. Simon's optimal two-stage design will be used to test the null hypothesis of pCR rate ≤5% and alternative hypothesis of pCR rate ≥15%, and 5 or more pCRs among 56 patients per arm are needed for the primary endpoint to be met. Secondary endpoints include major pathological response (MPR) rate, pCR/MPR rate in different EGFR mutation subgroups (19DEL or L858R) and different PD-L1 expression subgroups (TPS < 1% and ≥ 1%), event-free survival and safety and tolerability. Peripheral blood, stool and tissue samples will be obtained longitudinally at baseline, during perioperation and at follow-ups for exploratory analysis. Clinical trial information: NCT05962021 .