Alectinib as neoadjuvant treatment in potentially resectable stage III ALK-positive NSCLC: Final analysis of ALNEO phase II trial (GOIRC-01-2020-ML42316).

8015 Background: Stage III Non-Small Cell Lung Cancer (NSCLC) is a heterogeneous group of tumors with a wide spectrum of clinical presentations and no single definitive therapeutic approach. The role of neoadjuvant alectinib in stage III ALK-positive NSCLC is still unclear. Here, we present the final analysis of the phase II, open-label, single-arm, multicenter study aimed at investigating the activity and safety of alectinib in potentially resectable locally advanced stage III ALK-positive NSCLC patients (ALNEO trial, EUDRACT number 2020-003432-25). Methods: Treatment-naïve patients with potentially resectable stage III ALK-positive NSCLC, ECOG PS≤1 were registered to receive neoadjuvant alectinib for 2 cycles (8 weeks) followed by surgery and adjuvant alectinib for 24 cycles (96 weeks). The primary endpoint was major pathological response (MPR) by Blinded Independent Central Review (BICR). Secondary endpoints included pathological complete response (pCR) by BICR, objective response (OR), event-free survival (EFS), disease-free survival (DFS), overall survival (OS) and adverse events (AEs). According to the Simon’s design (P0=20%, P1=40%), 18 and 33 patients were required for the first and second stage, respectively. Results: A total of 33 patients were registered in 20 Italian Oncology Centers from May 2021 to July 2024. Median age was 62 years (Interquartile Range [IQR], 49–74 years), 23 (70%) patients were female and 17 (52%) were never smokers. Clinical stage according to the 8th AJCC TNM was IIIA in 21 (64%) and IIIB in 12 (36%) patients. The most represented stage was T3N2 (n=8, 24%), followed by T1aN2 (n=4, 12%), T2aN2 (n=4, 12%), T4N0 (n=4, 12%) and T4N2 (n=4, 12%). All the patients completed the neoadjuvant phase and 28 (85%) underwent surgery, which consisted of lobectomy in 21 (64%), pneumonectomy in 3 (9%) and other surgery in 4 (12%) patients. Among patients who completed surgery, R0 was achieved in 24 (86%) patients. According to the BICR, MPR was documented in 15 (46%, 90% Confidence Interval [CI]: 31%–61%) patients and pCR in 4 (12%, 95% CI: 3%–28%) patients. Overall, an OR was observed in 22 (67%) patients. Adjuvant treatment was started in 26 (79%) patients with a median interval from surgery of 5.1 weeks (IQR, 3.6–6.0 weeks). After a median follow-up of 15.2 months (IQR, 6.8–27.8 months), 31 (94%) patients were alive and 5 (19%) patients completed the adjuvant treatment. Median EFS and OS were not reached. A total of 6 (18%) patients experienced disease progression/recurrence. Grade≥3 AEs occurred in 3 (9%) and 2 (8%) patients during neoadjuvant and adjuvant phase, respectively. Conclusions: ALNEO study met its primary endpoint, suggesting alectinib as a feasible peri-operative option in resectable locally advanced stage III ALK-positive NSCLC patients. The study was partially supported by Roche S.p.A. Clinical trial information: NCT05015010 .