ALNEO Trial of Alectinib for ALK-Positive NSCLC Meets Primary Endpoint

The ALNEO study met its primary endpoint, suggesting that alectinib is a “feasible peri-operative option” for patients with resectable, locally advanced stage III ALK-positive non-small cell lung cancer (NSCLC), according to a final analysis of the trial presented at the 2025 American Society of Clinical Oncology Annual Meeting.

The phase 2 open-label, single-arm, multicenter study investigated lectinib in treatment-naïve patients with stage III ALK-positive disease to evaluate the feasibility and tolerability of the therapy.

From May 2021 to July 2024, 33 patients from 20 oncology centers in Italy were enrolled in the clinical trial. Most patients were women (70%), with a median age of 62 years. More than half (52%) of patients were never smokers and had an Eastern Cooperative Oncology Group Performance Status of 1 or less.

Twenty-one patients received a stage IIIa diagnosis, and 12 patients had stage IIIb. The most represented stage was T3N2 (n=8), followed by T1aN2 (n=4), T2aN2 (n=4), T4N0 (n=4), and T4N2 (n=4).

“Stage III NSCLC is a heterogeneous group of tumors with a wide spectrum of clinical presentations and no single definitive therapeutic approach,” said first author Alessandro Leonetti, MD, PhD, University Hospital of Parma, Parma, Italy.

Neoadjuvant alectinib was given for two cycles (8 weeks), followed by surgical resection and adjuvant alectinib for 24 cycles (96 weeks).

The primary endpoint was major pathological response (MPR) by blinded independent central review (BICR). Pathological complete response (pCR) by BICR, objective response (OR), event-free survival (EFS), disease-free survival, overall survival (OS), and adverse events (AEs) were secondary endpoints.

Surgical resection was done in 28 patients [lobectomy (n=21); pneumonectomy (n=3); and Other (n=4)] and R0 was achieved in 24 (86%) patients.

Furthermore, MPR occurred in 15 (46%), pCR in 4 (12%), and OR in 22 (67%) of patients.

At a median of 5.1 weeks post-surgery, adjuvant treatment was given to 26 (79%) patients. After a median follow-up of 15.2 months, 31 (94%) patients were alive, and 5 (19%) patients completed the adjuvant treatment. Median EFS and OS were not reached.

Treatment-related grade 3 or greater AEs occurred in five patients, three during the neoadjuvant phase and two during the adjuvant phase. The researchers observed disease progression or recurrence in 6 (18%) patients.