Firmonertinib Plus Chemotherapy for Unresectable EGFR PACC-Mutant Stage III Lung Cancer: A Phase II Study

Background: EGFR PACC mutations (P-loop and αC-helix compressing mutations) represent a distinct subtype of EGFR mutations with unique structural characteristics and potentially different responses to targeted therapies. There is an unmet clinical need for effective treatment regimens for patients with unresectable Stage III lung adenocarcinoma harboring these mutations. Firmonertinib is a highly selective third-generation EGFR-TKI with demonstrated efficacy. Combining targeted therapy with chemotherapy may provide synergistic anti-tumor effects. Study Design: This is a prospective, single-arm, multicenter Phase II clinical study. Eligible patients will receive Firmonertinib in combination with chemotherapy. Objectives: The primary objective of this study is to evaluate the objective response rate (ORR) of Firmonertinib combined with chemotherapy in this patient population. The secondary objectives include: To evaluate the 1-year and 3-year event-free survival (EFS) rates, surgical conversion rate, R0 resection rate, major pathological response (MPR), pathological complete response (pCR), event-free survival (EFS), and overall survival (OS).To assess the safety and tolerability of the combination regimen. Significance: This study aims to provide robust clinical evidence for the efficacy and safety of Firmonertinib combined with chemotherapy, potentially establishing a new therapeutic option for patients with unresectable EGFR PACC-mutant Stage III lung adenocarcinoma.