2500 - Biomarker Analysis of Iruplinalkib Combined with Chemoradiotherapy in ALK+ Unresectable Stage ? Non-Small Cell Lung Cancer
Presenter(s)
L. Wang1, B. Zou1, H. Zhou2, X. Zhang2, X. Meng1, A. Shi3, X. Liu4, Q. Guo2, J. Zhang2, C. Liu1, P. Song5, Q. Yu1, X. Hu1, J. Pang6, X. Zhang6, Y. Shao6,7, C. Zhu8, Y. Sang8, and J. Yu9; 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 2Department of Respiratory Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 3Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China, 4Department of Medical Oncology, Linyi Cancer Hospital, Linyi, China, 5Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 6Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China, 7School of Public Health, Nanjing Medical University, Nanjing, China, 8Qilu Pharmaceutical Co., Ltd., Shanghai, China, 9Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
Purpose/Objective(s): This study aimed to identify predictive biomarkers associated with the efficacy of iruplinalkib combined with chemoradiotherapy (CRT) in ALK+ unresectable stage ? non-small cell lung cancer (NSCLC), focusing on tumor genomics and circulating tumor DNA (ctDNA) dynamics.
Materials/Methods: This analysis includes 15 patients with ALK+ unresectable stage ? NSCLC from the INNOVATION trial (NCT05351320), whose tumor samples underwent next-generation sequencing. Tumor and plasma samples were collected at multiple time points: baseline, post-induction therapy, post-CRT, during maintenance therapy. A fixed MRD panel targeting the 2,365 cancer-relevant genes was used to analyze biomarkers, including ALK fusion variants, co-mutations, and ctDNA dynamics. Efficacy was assessed by overall response rate (ORR) and disease control rate (DCR) according to RECIST 1.1.
Results: From May 2022 to November 2024, 15 patients (median age 53 years; 80% never-smokers) were analyzed. Most patients (93%) were diagnosed with adenocarcinoma, and 80% were stage ?B or ?C disease. The most common ALK fusion variants were EML4-ALK V1 and V3 (80% of cases), with one novel MTHFD1L-ALK fusion identified. Nine patients received iruplinalkib induction followed by CRT and maintenance therapy, while six received CRT followed by iruplinalkib maintenance alone. Patients with EML4-ALK fusion had a 100% ORR (all partial responses). The patient with MTHFD1L-ALK showed stable disease (SD) and high tumor mutational burden (TMB) with co-mutations in PI3K and NRF2 pathways. Baseline ctDNA data was available for 10 patients. 80% (8/10) were ctDNA-positive. Among ctDNA-positive patients, 75% (6/8) achieved ctDNA clearance during treatment, all achieving PR. Patients without ctDNA clearance had a 50% ORR. One patient with persistently positive ctDNA and relapsed at 8.3 months since treatment.
Conclusion: ctDNA clearance during treatment is a promising predictive biomarker of response to iruplinalkib combined with chemoradiotherapy. Dynamic ctDNA monitoring provides early insights into treatment response and relapse.