NEW YORK – The US Food and Drug Administration on Friday approved AstraZeneca and Daiichi Sankyo's Trop-2-directed antibody drug conjugate Datroway (datopotamab deruxtecan) for the treatment of hormone receptor (HR)-positive, HER2-negative unresectable or metastatic breast cancer patients who had prior endocrine therapy and chemotherapy.
The approval was based on data from the Phase III TROPION-Breast01 trial, which assessed Datroway versus investigator's choice of chemotherapy in 732 patients. The TROPION-Breast01 trial included patients who were HER2-negative and HER2-low, defined as having immunohistochemistry (IHC) scores of 0, 1+, or 2+ and negative in situ hybridization (ISH) results. In its approval, the FDA also defined HER2-negative as IHC 0, IHC1+, or IHC 2+ and ISH negative, the same as the trial.
In the trial, Datroway demonstrated an improvement in progression-free survival, 6.9 months, versus 4.9 months in the chemo arm. However, the overall survival result was not statistically significant, with median overall survival of 18.6 months on Datroway and 18.3 months on chemo.
The objective response rate in the Datroway arm was 36 percent and the median duration of response was 6.7 months, compared to a response rate of 23 percent and duration of response of 5.7 months in the chemotherapy arm.
Datroway was approved in this indication in Japan last month. The companies are also evaluating Datroway as a monotherapy and in combination with immunotherapy in patients with triple-negative breast cancer or HR-low, HER2-negative breast cancer.
The firms are also studying Datroway as a treatment for non-small cell lung cancer. However, after feedback from regulators and withdrawing applications seeking approval in the US and EU for an all-comer population, the companies are now pursuing approval for Datroway in previously treated locally advanced or metastatic EGFR-mutant NSCLC. In December, the FDA granted breakthrough therapy designation to the drug in this setting.