On April 18, 2024, the U.S. Food and Drug Administration (FDA) approved alectinib (Alecensa®) for adjuvant treatment following tumor resection in patients with anaplastic lymphoma kinase (ALK)–positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test.

FDA update

Efficacy was demonstrated in a global, randomized, open-label trial (ALINA, NCT03456076) in patients with ALK-positive NSCLC who had complete tumor resection. Eligible patients were required to have resectable stage IB (tumors ≥ 4 cm) to IIIA NSCLC (by the AJCC Cancer Staging Manual, seventh edition) with ALK rearrangements identified by a locally performed FDA-approved ALK test or by a centrally performed VENTANA ALK (D5F3) CDx assay. A total of 257 patients were randomized 1:1 to receive alectinib 600 mg orally twice daily or platinum-based chemotherapy following tumor resection.

The major efficacy outcome measures were investigator-assessed disease-free survival (DFS) in patients with stage II–IIIA NSCLC and DFS in the overall stage IB–IIIA study population. In patients with stage II–IIIA NSCLC, median DFS was not reached (95% CI not estimable) in the alectinib arm and 44.4 months (95% CI: 27.8, not estimable) in the chemotherapy arm (HR = 0.24; 95% CI = 0.13, 0.45; p < 0.0001). The overall study population had similar results, with median DFS not reached (95% CI not estimable) in the alectinib arm and 41.3 months (95% CI = 28.5, not estimable) in the chemotherapy arm (HR = 0.24; 95% CI = 0.13, 0.43; p < 0.0001).

The most common adverse reactions reported in patients at least 20% of patients taking alectinib in the drug’s clinical trials were hepatotoxicity, constipation, myalgia, COVID-19, fatigue, rash, and cough.

The recommended alectinib dose is 600 mg orally twice daily with food for two years or until patients experience disease recurrence or unacceptable toxicity. FDA said it will post the full prescribing information for alectinib’s new indication here.

FDA’s review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, Israel’s Ministry of Health, Switzerland’s Swissmedic, and United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at other regulatory agencies involved with Project Orbis.

The applicant used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid. FDA approved the application one month ahead of the FDA goal date.

The application was granted priority review and orphan drug designation. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.