Intrathecal sintilimab for leptomeningeal metastases of non-small cell lung cancer failed from targeted therapy and intrathecal chemotherapy (LMIS study)

Abstract Background Leptomeningeal metastases (LMs) are serious complications of non-small cell lung cancer (NSCLC). This study aimed to investigate the safety and efficacy of intrathecal immune checkpoint inhibitors (ICIs) in treating NSCLC-LM. Methods We conducted this prospective phase 1 study (ChiCTR2200062245) using a traditional “3+3” design with intrathecal sintilimab (dose escalation 10, 20, 30, and 40 mg) for NSCLC-LM patients who had progressed from targeted therapy and intrathecal pemetrexed. The primary study endpoints were safety and recommended dose, and the secondary endpoints included clinical response rate, progression-free survival (PFS), intracranial progression-free survival (iPFS), and overall survival (OS). Results No dose-limiting toxicity was found at 10, 20, 30, and 40 mg for intrathecal sintilimab. Therefore, sintilimab 40 mg was recommended for intrathecal injection. A total of 19 patients were enrolled in this study. The median age at diagnosis of LM was 53 years. The overall incidence of adverse events (AEs) was 68.4%, and rash (n = 4, 21.1%) was the most common AEs, which returned to normal after symptomatic treatment. As 1 patient was lost to follow-up and 18 patients could be evaluated for efficacy, the clinical response rate was 38.9% (7/18). Median PFS was 3.5 months (95% CI: 2.7–4.2 months), median iPFS was 3.5 months (95% CI: 1.3–5.6 months), and median OS was 11.5 months (95% CI: 0.0–25.4 months). Conclusions Intrathecal ICIs for NSCLC-LM patients are safe, and the recommended dose of sintilimab is 40 mg. Intrathecal sintilimab for NSCLC-LM failed from multi-line therapies, showed potential effectiveness in some patients, and is worthy of further study.