FDA Approves CDx for Lorlatinib in ALK-Positive Non–Small Cell Lung Cancer

The FDA has granted approval to the VENTANA ALK (D5F3) CDx Assay as a companion diagnostic (CDx) to identify patients with ALK-positive non–small cell lung cancer (NSCLC) who may be eligible for treatment with the recently approved ALK inhibitor lorlatinib (Lorbrena), announced Roche, in a press release.1

Approval of this CDx makes the VENTANA ALK CDx Assay the only immunohistochemistry (IHC) test approved by the FDA as a CDx for lorlatinib.1

"This FDA approval is great news for ALK-positive patients," said Jill German, head of Roche Pathology Customer Segment, in a statement. "It is essential that we identify patients with this cancer biomarker quickly and accurately so they can be treated with effective targeted therapy. This label expansion advances Roche's commitment to personalized healthcare by providing lung cancer patients with access to more treatment options and a better chance for progression-free survival compared to the standard of care."

Lorlatinib was recently granted an expanded approval by the FDA. The expansion includes an indication for the first-line treatment of patients with ALK-positive NSCLC. Previously, the third-generation ALK inhibitor was approved for the treatment of patients with ALK-positive NSCLC whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib (Alecensa) or ceritinib (Zykadia) as the first ALK inhibitor therapy for metastatic disease.

The FDA made the decision to expand the approval of the agent based on data from the phase 3 CROWN study of 296 patients, which demonstrated a significant reduction in the risk of progression or death for patients with previously untreated ALK-positive NSCLC with lorlatinib compared with crizotinib (Xalkori). At 12 months, the lorlatinib arm had 78% of patients (95% CI, 70%-84%) alive without disease progression versus 39% (95% CI, 30%-48%) in the crizotinib arm (HR, 0.28; 95% CI, 0.19-0.41; P < .001).2

The VENTANA ALK CDx Assay qualitatively detects ALK protein in formalin-fixed, paraffin-embedded NSCLC tissue with the aid of a staining instrument. The assay showed superiority to the standard fluorescence in situ hybridization (FISH) test, Vysis ALK-break-apart FISH-Probe KIT in terms of predictive value. The assays were compared in 29 patients with ALK-positive NSCLC who were diagnosed using both FISH and IHC biopsies. The assays were intended to determine the predictive value of response to the ALK inhibitor crizotinib. The analysis showed that the VENTANA ALK CDx Assay was more accurate in showing both tumor response and improvement in PFS in patients receiving crizotinib compared with the Vysis ALK-break-apart FISH-Probe KIT. The tumor response area under the curve (AUC) was 0.86 versus 0.64, respectively for a P value of 0.03. The AUC for progression-free survival was 0.86 versus 0.36, respectively (P = .005). Finally, the overall survival AUC was 0.78 with the VENTANA ALK CDx Assay versus 0.41 with the Vysis ALK-break-apart FISH-Probe KIT (P = .01).1,3

In addition to lorlatinib, the VENTANA ALK CDx Assay is an FDA-approved CDx to identify patients who may derive benefit from treatment with crizotinib, ceritinib, and alectinib for ALK-mutant NSCLC.

The assay is available in the United States for use with the BenchMark ULTRA and BenchMark XT IHC/in situ hybridization staining instruments.

_References:

_{1. Roche receives FDA approval for VENTANA ALK (D5F3) CDx Assay to identify lung cancer patients eligible for targeted treatment with LORBRENA (lorlatinib). News release. Roche. March 9, 2021. Accessed March 9, 2021.}

_{2. U.S. FDA expands approval of Pfizer’s Lorbrena® as first-line treatment for ALK-positive metastatic lung cancer. News release. Pfizer. March 3, 2021. Accessed March 9, 2021. https://bit.ly/2PnGbpF}

_{3. Wekken AJ, Pelgrim R, Hart N, et al. Dichotomous ALK-IHC is a better predictor for ALK inhibition outcome than traditional ALK-FISH in advanced non-small cell lung cancer. Clin Cancer Res. 2017: 23(15);4251-4258. doi: 10.1158/1078-0432.CCR-16-1631.}