Abstract 967TiP
Background
Survival outcomes of locally advanced non-small cell lung cancer (LA-NSCLC) are unfavorable and benefit from perioperative chemotherapy is only around 5%. Recently, promising results with neoadjuvant immunotherapy and targeted therapy have been shown. However, almost all the clinical trials are looking for eligible patients for certain drugs, instead of seeking suitable treatments for certain patients. Therefore, we are carrying out the first umbrella trial on precise neoadjuvant therapy for resectable LA-NSCLCs based on next-generation sequencing (NGS) and multidisciplinary team (MDT).
Trial design
The PURPOSE trial (ChiCTR2100053021) is an open-label, prospective, phase II, umbrella trial evaluating the efficacy and safety of precise neoadjuvant therapy based on NGS and MDT for LA-NSCLCs. Eligible patients (Age 18-75 years, resectable stage II-IIIB NSCLC, no prior therapy, ECOG PS 0-1) will be divided into six independent cohorts based on NGS. In detail, EGFR 19del will receive Almonertinib. EGFR 21L858R will receive Furmonertinib. EGFR rare mutations (T790M/G719X/S768I/L861Q) will receive Osimertinib. Other mutations include ALK/MET/RET/HER2 (Ensartinib for ALK, Savolitinib for MET, Pralsetinib for RET, Pyrotinib for HER2). For mutation-negative patients, PD-L1≥1% will receive Camrelizumab with chemotherapy and PD-L1<1% will receive chemotherapy only. Patients refusing this trial will be enrolled into a real-world study cohort. Neoadjuvant therapy will be performed for Q3W, 3 cycles. 26 patients will be enrolled independently into each cohort in a Simon`s mini-max two-stage design with total 156 participants for the entire trial. Imaging evaluation of treatment response will be conducted within 2 weeks after neoadjuvant therapy by MDT and surgery will be performed within 4-6 weeks after neoadjuvant therapy. Adjuvant therapy will be decided by MDT according to the current guidelines. The primary endpoint is ORR. The secondary endpoints include pCR, MPR, EFS, DFS, OS, R0 rate, perioperative outcomes. The exploratory endpoint is to investigate the relationship between oncological prognosis and minimal residual disease (MRD).
Clinical trial identification
ChiCTR2100053021.
Editorial acknowledgement
Under the guidance of authors, assistance in medical writing and editorial support was provided by Jiangsu Hengrui Medicine.
Legal entity responsible for the study
Shanghai Chest Hospital.
Funding
Allist Pharmaceuticals, AstraZeneca, Betta Pharmaceuticals, Burning Rock Biotech, CStone Pharmaceuticals, Hansoh Pharmaceuticals, Jiangsu Hengrui Medicine.
Disclosure
All authors have declared no conflicts of interest.