NEW YORK – AstraZeneca and Daiichi Sankyo last week said they have voluntarily withdrawn an application seeking approval in the EU for their TROP2-directed antibody-drug conjugate (ADC) datopotamab deruxtecan in metastatic nonsquamous non-small cell lung cancer.
The decision to withdraw the marketing authorization application is based on the results of the Phase III TROPION-Lung01 clinical trial, in which the drugmakers randomized roughly 600 NSCLC patients with and without actionable genomic alterations to receive either datopotamab deruxtecan (Dato-DXd) or docetaxel chemotherapy. If patients' tumors harbored actionable genomic alterations, they had to have previously received an approved targeted therapy and platinum-based chemotherapy. If they did not have actionable genomic alterations, they had to have previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.
Although patients on the ADC had better median progression-free survival compared to chemo, the difference in median overall survival between the two arms was not statistically significant. In all comers with nonsquamous NSCLC, the median overall survival was 14.6 months with Dato-DXd versus 12.3 months with chemotherapy. In withdrawing the application, AstraZeneca and Daiichi Sankyo considered feedback from the European Medicines Agency' Committee for Medicinal Products for Human Use.
The companies' actions in Europe follow a similar decision in the US. In November, the firms announced they would no longer seek the US Food and Drug Administration's approval for Dato-DXd in an all-comer nonsquamous NSCLC population. Instead, AstraZeneca and Daiichi Sankyo, who codevelop Dato-DXd, said they would seek FDA approval for the ADC in NSCLC patients with EGFR-mutated tumors.
The firms said in a statement that they are still seeking approval in the EU for Dato-DXd as a treatment for hormone receptor-positive, HER2-negative metastatic breast cancer based on the Phase III TROPION-Breast01 clinical trial.