FDA Grants Priority Review to Alectinib for ALK+ NSCLC

The FDA is expected to make a decision for approval by May 22, 2024. If approved, alectinib will be the first and only ALK inhibitor available for patients with early-stage ALK-positive NSCLC

The FDA has accepted a supplemental biologics license application (sBLA) and granted priority review for the ALK inhibitor alectinib (Alecensa) as an adjuvant treatment following surgery for patients with early-stage ALK-positive non–small cell lung cancer (NSCLC).¹

The decision was based on the results from the phase 3 ALINA study (NCT03456076).² Patients who received alectinib experienced a 76% decrease in the risk of disease recurrence or death compared with patients who received platinum-based chemotherapy death (HR, 0.24; 95% CI, 0.13-0.43; P < .0001). At the time of follow up, median disease-free survival (DFS) was not reached in the experimental arm vs 41.3 months for the chemotherapy arm (95% CI, 28.5-not evaluable [NE]).

In addition, a clinically meaningful improvement of central nervous system (CNS) DFS was also observed (HR, 0.22; 95% CI, 0.08-0.58).

“These potentially practice-changing data reinforce the potential of [alectinib] as a new standard of care in the ALK-positive early lung cancer setting where treatment options are currently extremely limited,” lead study author Benjamin Solomon, MBBS, PhD, FRACP, medical oncologist and professor at Peter MacCallum Cancer Centre, Australia, stated in a news release. “The magnitude of disease-free survival observed in this study could represent a paradigm shift in the way we manage early-stage ALK-positive lung cancer.”

This randomized, multicenter, open-label, phase 3 study included a total of 255 patients completely resected stage IB (tumor ≥ 4 cm) to IIIA (UICC/AJCC 7th edition) ALK-positive NSCLC.³ Patients were randomized 1:1 to receive either 600 mg of alectinib twice daily for 24 months or four 21-day cycles of platinum-based chemotherapy. Treatment was administered until planned completion, disease recurrence, unacceptable toxicity, withdrawal of consent, or death.

Eligibility to enroll on the trial included having completely resected stage IB to IIIA disease and an ECOG performance status of 0 to 1. Patients who received prior adjuvant radiotherapy for NSCLC or prior exposure to systemic anti-cancer treatment and ALK inhibitors could not enroll on the trial. Stratification factors included disease stage and race.

The primary end point for this study was DFS. Data on the secondary endpoint of overall survival were immature at the time of analysis.

The safety profile and tolerability of alectinib were consistent with previous trials in the metastatic setting, and no new safety findings were observed. In the primary analysis, data showed that grade 3 or 4 adverse effects (AEs) occurred in 30% of patients who received alectinib and 31% of patients who received chemotherapy. No grade 5 AEs were reported in either arm. A total of 5.5% of patients in the experimental arm and 12.5% in the chemotherapy arm discontinued treatment due to AEs.

The FDA is expected to make a decision for approval by May 22, 2024. If approved, alectinib will be the first and only ALK inhibitor available for patients with early-stage ALK-positive NSCLC. The application will be reviewed using its new Real-Time Oncology Review pilot program, which was finalized in November 2023.

References:

1. FDA Grants Priority Review for Alecensa as First ALK Inhibitor for Early-Stage Lung Cancer. News release. Genentech. January 29, 2024. Accessed January 29, 2024.
2. Genentech’s Alecensa Reduces the Risk of Disease Recurrence or Death by an Unprecedented 76% in People With ALK-Positive Early-Stage Non-Small Cell Lung Cancer. News release. Genentech. October 17, 2023. Accessed January 29, 2024.http://tinyurl.com/ummj8exu
3. Solomon BJ, Ahn JS, Barlesi F, et al. ALINA: a phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol. 2019;37(15_suppl):TPS8569-TPS8569. doi:10.1200/jco.2019.37.15