NEW YORK – AstraZeneca on Friday said that the TROPION-Breast01 Phase III trial of Dato-DXd (datopotamab deruxtecan) has demonstrated a significant and clinically meaningful improvement in progression free survival compared to investigator's choice of chemotherapy in patients with advanced HR-positive, HER2-low or -negative breast cancer.
The company plans to share the results of the trial with health authorities.
In the trial, investigators are evaluating the safety and efficacy of Dato-DXd in 733 patients who are stratified into groups based on the number of prior lines of chemotherapy (up to two), prior use of CDK4/6 inhibitors, and geographic region. The primary outcome measures of the trial are progression free survival and overall survival. Secondary outcome measures include objective response rate, duration of response, and disease control rate. To be eligible for the trial, patients must have HER2-low or -negative breast cancer measured as a HER2 score of IHC 0, IHC1+, or IHC2+ with a negative FISH result.
AstraZeneca said it also saw a trend toward improved overall survival for Dato-DXd versus chemotherapy in the trial, but the data were not mature at the time of the interim analysis. The safety profile of the drug was consistent with what researchers saw in previous clinical trials.
Dato-DXd is an antibody drug conjugate targeting TROP2 jointly developed by AstraZeneca and Daiichi Sankyo. The companies are also evaluating Dato-DXd in two additional Phase III trials in breast cancer. In TROPION-Breast02, they are comparing Dato-DXd to chemotherapy in patients with previously untreated advanced triple negative breast cancer, and in TROPION-Breast03 they are evaluating Dato-DXd with and without Imfinzi (durvalumab) compared to investigator's choice of therapy in patients with early stage triple negative breast cancer with residual disease following neoadjuvant therapy.
These trials are part of a strategy AstraZeneca announced in July to replace chemotherapy in the late-line breast cancer setting across all disease subtypes with its targeted therapies, including Enhertu (trastuzumab deruxtecan) and Dato-DXd.