FDA Gives Green Light to Companion Diagnostic for Brigatinib in ALK+ NSCLC

The FDA has approved FoundationOne CDx for use as a companion diagnostic for brigatinib, which was approved for the treatment of adult patients with ALK-positive, metastatic non–small cell lung cancer.

The FDA has approved FoundationOne CDx for use as a companion diagnostic for brigatinib (Alunbrig), which was approved for the treatment of adult patients with ALK-positive, metastatic non–small cell lung cancer (NSCLC).1

The assay is the only tissue-based comprehensive genomic profiling test that has received approval from the regulatory agency and can now be used to identify ALK-positive metastatic NSCLC and determine patients who can be candidates for brigatinib, which can be used in a first or later line of therapy.

“We are excited by the approval of FoundationOne CDx as a companion diagnostic for [brigatinib], an important milestone in the diagnosis and treatment of people living with ALK-positive NSCLC,” Dion Warren, head of US Oncology Business Unit at Takeda, stated in the press release. “The approval of FoundationOne CDx to inform treatment with [brigatinib] is the first of 3 companion diagnostics in development as part of our ongoing partnership between Foundation Medicine and Takeda aimed at addressing the urgent need for broad access to genomic tests and expanding treatment options for people with lung cancer.”

The assay is designed to produce clinically actionable information so that appropriate therapies can be considered based on the genomic profile of each patient’s cancer.2 Test results can include information on microsatellite instability and tumor mutational burden to inform decisions regarding immunotherapy. The assay also can produce data on loss of heterozygosity in patients with ovarian cancer.

In May 2020, the FDA approved brigatinib for the frontline treatment of patients with ALK-positive metastatic NSCLC.3 The decision was based on the phase 3 ALTA-1L trial (NCT02737501).

At a median follow-up of 24.9 months, brigatinib was superior to crizotinib (Xalkori) with regard to progression-free survival (PFS) per blinded independent review committee (BIRC) assessment.4 The median PFS in the investigative and control arms was 24.0 months and 11.0 months (HR, 0.49; 95% CI, 0.35-0.68; log-rank P <.0001).4 The investigator-assessed PFS with brigatinib vs crizotinib was 29.4 months and 9.2 months, respectively (HR, 0.43; 95% CI, 0.31-0.61).

The open-label phase 3 trial enrolled adult patients with locally advanced/metastatic NSCLC and at least 1 measurable lesion per RECIST v1.1 criteria who did not previously receive ALK-targeted therapy. Notably, patients were allowed to have asymptomatic or stable central nervous system metastases.

Study participants were randomized 1:1 to receive a daily dose of brigatinib at 180 mg with a 7-day lead-in at a once-daily dose of 90 mg or crizotinib at a twice-daily dose of 250 mg. Treatment was administered until disease progression, unacceptable toxicity, or until they met other discontinuation criteria. Notably, crossover from crizotinib to brigatinib was permitted following BIRC-assessed progression.

The primary end point was BIRC-assessed PFS, and secondary end points comprised BIRC-assessed confirmed objective response rate (ORR), confirmed intracranial ORR, intracranial PFS, overall survival (OS), duration of response (DOR), and safety, among others.

Baseline characteristics were balanced between the 2 treatment arms with regard to age, sex, ECOG performance status, presence or absence of brain metastases, previous radiotherapy or chemotherapy, and best response to chemotherapy.

As of June 18, 2019, 55% of those on the investigative arm and 17% of those on the control arm were still receiving treatment. The median follow-up with brigatinib was 24.9 months (range, 0-34.1) and 15.2 months (range, 0.1-36.0) with crizotinib. The median duration of treatment in the investigative and control arms was 24.3 months (range, 0.1-34.6%) and 8.4 months (range, 0.1-36.0).

Additional data showed that the 2-year probability of not experiencing progression with brigatinib was 48% vs 26% with crizotinib per BIRC assessment; these rates were 56% and 24%, respectively, per investigator assessment. The PFS improvements observed via BIRC evaluation proved to be consistent across patient subsets.

The ORR per BIRC assessment was 74% (95% CI, 66%-81%) with brigatinib vs 62% (95% CI, 53%-70%) with crizotinib. The median DOR in the investigative and control arms had not been reached vs 13.8 months (range, 9.3-20.8), respectively.

Seventy patients died, as of the data cutoff date; 24% of these patients received brigatinib and 27% received crizotinib. The 2-year OS probability rates in the investigative and control arms were 76% (95% CI, 67%-82%) and 74% (95% CI, 65%-80%), respectively (HR, 0.92; 95% CI, 0.57-1.47; log-rank P = .771)

Of the patients with brain metastases at baseline (n = 81), 40 were in the brigatinib arm and 41 were in the crizotinib arm. The BIRC-evaluated non-progression probability rates in the investigative and control arms at 2 years were 43% and 10%, respectively (HR, 0.25; 95% CI, 0.14-0.46; log-rank P <.001).

Regarding safety, the most frequent any-grade treatment-emergent adverse effects (TEAEs) were gastrointestinal effects, increased blood creatinine phosphokinase, cough, and increased aminotransferase. Seventy-three percent of patients in the brigatinib arm experienced TEAEs that were grade 3 to 5 vs 61% of those in the crizotinib arm.

Five percent of 136 patients on the brigatinib arm vs 2% of 137 patients on the crizotinib arm experienced interstitial lung disease (ILD) or pneumonitis; 3% vs less than 1% of patients experienced grade 3 or 4 effects. Any-grade early-onset ILD or pneumonitis was observed in 3% vs 2% of those in the brigatinib and crizotinib arms, respectively.


  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 1, 2021. https://bit.ly/3Ah3KUa
  2. FoundationOne CDx. Foundation Medicine. Accessed July 1, 2021. https://bit.ly/3qE4r5q
  3. US FDA approves Takeda’s ALUNBRIG® (brigatinib) as a first-line treatment option for patients diagnosed with rare and serious form of lung cancer. News release. Pharmaceutical Company Limited. May 22, 2020. Accessed July 1, 2021. https://bit.ly/3gc8qk5
  4. Camidge DR, Kim HR, Ahn M-J, et al. Brigatinib versus crizotinib in advanced ALK inhibitor–naïve ALK-positive non–small cell lung cancer: second interim analysis of the phase III ALTA-1L trial. J Clin Oncol. 2020;38(31):3592-3603. doi:10.1200/JCO.20.00505