FDA Approves FoundationOne CDx as a Companion Diagnostic for Brigatinib in ALK+ Metastatic NSCLC

FoundationOne CDx, a comprehensive genomic profiling test, has been approved for use in conjunction with brigatinib to test for solid tumors in patients with ALK-positive NSCLC.

FoundationOne CDx has been approved by the FDA as a companion diagnostic for brigatinib (Alunbrig) in the treatment of patients with anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC), according to a press release from Foundation Medicine, Inc.1

FoundationOne CDx is a tissue-based comprehensive genomic profiling (CGP) test for solid tumors that can identify patients with ALK-positive NSCLC who are eligible for treatment with brigatinib. Brigatinib is a tyrosine kinase inhibitor (TKI) that is designed to target ALK molecular alterations and is approved as a first-line treatment therapy.

“We are excited by the approval of FoundationOne CDx as a companion diagnostic for ALUNBRIG, an important milestone in the diagnosis and treatment of people living with ALK+ non-small cell lung cancer,” said Dion Warren, head, U.S. Oncology Business Unit, Takeda.

In May of 2020, the FDA approved brigatinib for the frontline treatment of ALK-positive metastatic NSCLC. The approval was based on the phase 3 ALTA-1L trial (NCT02737501) in which the agent yielded a 76% reduction in risk of disease progression or death in patients with newly diagnosed disease with no brain metastases, according to the study’s 2-year investigator-assessed results.2

Patients who were treated with brigatinib had an estimated median progression-free survival (PFS) 24 months (95% CI: 18.5–not evaluable) vs 11 months (95% CI: 9.2-12.9) for those treated with crizotinib (Xalkori; HR, 0.49; 95% CI: 0.35-0.68; P< .0001).

Enrollment included 275 patients (n=137) in the brigatinib group, wherein patients received 90 mg orally for the first 7 days and then increased to 180 mg orally once daily. In the crizotinib group (n=138), patients received 250 mg orally twice daily. Investigators used a Vysis ALK Break Apart Fish Probe Kit to test a subset of clinical samples. Of the enrolled patients, 239 had positive results utilizing the Vysis diagnostic test. Additionally, 20 patients had negative restuls and 16 were unavailable.

The primary end point of the study was progression-free survival (PFS), with a key secondary end point of overall response rate (ORR).

Patients treated with brigatinib had an ORR of 74% (95% CI: 66%-81%), vs 62% (95% CI: 53%-70%) for patients treated with crizotinib.

Some of the most common adverse effects with brigatinib were diarrhea, fatigue, nausea, rash, or cough, all of which occurred 25% or more of the time.

Speaking on the approval of FoundationOne CDx, chief executive officer at Foundation Medicine Brian Alexander, MD, MPH stated, “This approval reinforces the importance of comprehensive genomic profiling in patient care and confirms its value in guiding treatment decisions at diagnosis of metastatic non-small cell lung cancer.”

FoundationOne CDx, a next-generation sequencing tool, is able to detect substitutions, insertions, and deletions, as well as copy number alterations in 324 genes and select gene rearrangements. Additionally, it can detect genomic signatures such as microsatellite instability and tumor mutational burden utilizing DNA isolated from formalin-fixed, paraffin-embedded tumor tissue specimens Although comprehensive genomic profiling can provide tumor mutation profiling and detect ALK positivity in this patient population, investigators caution that there is no guarantee that patients will be matched to a treatment, and that a negative test result does not rule out the presence of an alteration.


1. FoundationOne®CDx receives FDA-approval as a companion diagnostic for ALUNBRIG® (brigatinib) to identify patients with ALK positive metastatic non-small cell lung cancer. News Release. Foundation Medicine. July 1, 2021. Accessed July 6, 2021. https://bit.ly/3ytHLb2

2. FDA approves brigatinib for ALK-positive metastatic NSCLC. News Release. FDA. May 26, 2020. Accessed July 6, 2021. https://bit.ly/3dPZ6mB