Abstract 179TiP
Background
Surgical resection, combined with or without perioperative immunochemotherapy is the standard treatment for early-stage non-small cell lung cancer (NSCLC), but its efficacy in ALK-rearranged (ALK+) patients remains limited. The development of ALK tyrosine kinase inhibitors (TKIs) revolutionized targeted therapy for ALK+ advanced NSCLC, significantly improving survival prognosis, with the ALINA study further advancing progress in postoperative adjuvant therapy. Lorlatinib, a potent third-generation ALK-TKI, provides superior CNS penetration and broader mutation coverage, making it particularly effective in advanced NSCLC. However, its potential as a neoadjuvant treatment in early-stage ALK+ NSCLC remains unexplored, warranting further investigation.
Trial design
This is a phase II, open-label, single-arm, prospective, multi-center study designed to evaluate the efficacy and safety of lorlatinib as a neoadjuvant treatment in patients with surgically resectable stage IB-IIIB ALK-rearranged NSCLC. The study plans to enroll 25 patients across 6 sites in China. Eligible patients will be those aged ≥18 years with histologically/cytologically confirmed lung adenocarcinoma, documented ALK-rearrangement mutation positive, and ECOG PS 0-1. Patients will receive lorlatinib 100 mg once daily for 6-8 weeks (determined by clinicians’ decision based on clinical practice) as neoadjuvant therapy, followed by surgical resection. The primary endpoint of the study is pathological complete response (pCR), while secondary endpoints include major pathologic response (MPR), objective response rate (ORR) per RECIST 1.1, surgical outcomes, rate of lymph node downstaging, and safety/tolerability. Exploratory objectives include the correlation between biomarkers and response/outcomes. The first patient had been enrolled in November, 2024 and last patient last visit will be in October, 2026.
Clinical trial identification
NCT06682884.
Editorial acknowledgement
Medical writing and editorial support were provided by Clinflash Healthcare Technology (Jiaxing) Co., Ltd.
Legal entity responsible for the study
The authors.
Funding
Pfizer Inc.
Disclosure
All authors have declared no conflicts of interest.