NEW YORK – AstraZeneca said Monday the US Food and Drug Administration granted priority review for its biologics license application for the TROP2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) it codeveloped with Daiichi Sankyo as a treatment for patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer who have progressed on or after treatment with an EGFR tyrosine kinase inhibitor and platinum-based chemotherapy.
In making its decision, the regulator considered data from the Phase II TROPION-Lung05 trial with supporting data from the Phase III TROPION-Lung01 trial. In TROPION-Lung05, AstraZeneca is evaluating Dato-DXd in patients with advanced NSCLC whose tumors have one or more genomic alterations, including in EGFR, ALK, ROS1, NTRK, BRAF, RET, or MET. In TROPION-Lung01, researchers are comparing treatment with Dato-DXd to docetaxel in advanced NSCLC patients with and without actionable genomic alterations.
In a pooled analysis of data from 117 patients in the two trials, those with previously treated advanced or metastatic EGFR-mutated NSCLC on Dato-DXd had an objective response rate of 42.7 percent. Five patients, or 4.3 percent, had complete responses, and 43 patients, or 38.5 percent, had partial responses. Another 48 patients, or 41 percent, had stable disease. The median duration of response was seven months, and the disease control rate was 86.3 percent. Patients survived a median 5.8 months without disease progression or death, and the median overall survival was 15.6 months.
"Treating advanced EGFR-mutated non-small cell lung cancer presents a significant challenge due to the limited efficacy of available treatments once the disease has progressed following front-line therapies, including the use of an EGFR-tyrosine kinase inhibitor," Daiichi Sankyo Global Head of R&D Ken Takeshita said in a statement. "If approved, datopotamab deruxtecan could become the first TROP2-directed antibody drug conjugate for lung cancer, providing a promising option for patients."
The FDA is expected to make a decision on approving the application in the third quarter of 2025.
In December 2024 the companies voluntarily withdrew an application for Dato-DXd in the European Union as a treatment for patients with advanced or metastatic nonsquamous NSCLC based on results from the TROPION-Lung01 trial that showed no statistically significant difference in median overall survival between patients given the ADC versus those treated with chemo.