Neoadjuvant and adjuvant iruplinalkib in resectable <i>ALK</i> or <i>ROS1</i> fusion-positive, non-small cell lung cancer (NSCLC): The preliminary results of the single-arm, exploratory Neo-INFINITY study.

e20044 Background: The ALNEO, NAUTIKA1, and SAKULA studies found perioperative alectinib and ceritinib were effective for resectable ALK -positive NSCLC. The Neo-INFINITY study aimed to evaluate the efficacy and safety of perioperative iruplinalkib for resectable ALK - or ROS1 -positive NSCLC. Here, the preliminary results of Stage 1 were reported. Methods: This single-arm phase II trial was conducted in China. Adult patients with pathologically confirmed resectable ALK - or ROS1 -positive NSCLC at stage IB–IIIA or IIIB (T3N2M0 only), ≥one measurable lesion via RECIST v1.1, ECOG performance status of 0 or 1 were eligible. Patients received neoadjuvant iruplinalkib orally at 180 mg/day (with a 7-day lead-in at 60 mg/day) for eight weeks, followed by surgery and then adjuvant iruplinalkib (the same dose and lead-in). The total treatment period was up to two years. The primary endpoint was major pathologic response (MPR). Simon's optimal two-stage design was implemented. The study would be stopped early if ≤one of eight patients achieving MPR at Stage 1. Another 18 patients would be enrolled at Stage 2. Results: From Feb 2023 to Jun 2024, 10 patients were enrolled. Two are still on neoadjuvant treatment, and eight patients who completed neoadjuvant treatment and surgery were included for analysis. Median age was 59 years (range 35–78). Two (25%) were male. One (12%) had squamous cell carcinoma, and ALK fusions were found in six (75%) patients. MPR and pathologic complete response (pCR) were achieved in four (50%) and two (25%) of eight patients, respectively. Among six ALK -positive cases, four (67%) patients obtained MPR, and two (33%) reached pCR. Objective response was observed in all eight (100%) patients. Radiologic downstaging was found in four (50%) patients. All patients underwent R0 resection. During iruplinalkib treatment, ≥grade 3 iruplinalkib-related adverse events (AE) were reported in two (25%) patients, the most common of which were alanine aminotransferase increased (two [25%]) and aspartate aminotransferase increased (one [12%]). Serious AE, iruplinalkib-related AE leading to dose interruption, reduction, and discontinuation occurred in zero, one (12%), one (12%), and zero patient, respectively. Conclusions: Neoadjuvant iruplinalkib is effective and feasible for resectable ALK - or ROS1 -positive NSCLC, with acceptable safety profiles. Stage 2 of the study is ongoing, and long-term results are awaited. Clinical trial information: NCT05765877 . Efficacy endpoints. Endpoints All patients (n=8) ALK -positive patients (n=6) Major pathologic response 4 (50%) 4 (67%) Pathologic complete response 2 (25%) 2 (33%) Objective response 8 (100%) 6 (100%) Radiologic downstaging 4 (50%) 2 (33%) R0 resection 8 (100%) 6 (100%) Note: Data are presented as n (%).