Skip to main content
Premium Trial:

Request an Annual Quote

Daiichi Sankyo, AstraZeneca Begin Two Phase III Dato-DXd Trials in TNBC

NEW YORK – Daiichi Sankyo and AstraZeneca on Monday said they began two Phase III trials of investigational TROP2 directed antibody-drug conjugate, datopotamab deruxtecan (dato-DXd), in combination with AstraZeneca's anti-PD-1 therapy, durvalumab, in two types of breast cancer.

One of the trials, called TROPION-Breast04, is evaluating neoadjuvant dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy in patients with stage II-III triple-negative breast cancer or hormone receptor (HR)-low and HER2-low or HER2-negative breast cancer.

Researchers will compare the neoadjuvant and adjuvant dato-DXd plus durvalumab combinations to Merck's Keytruda (pembrolizumab) plus chemotherapy in this setting. The TROPION-Breast04 study will include more than 1,700 patients. The firms aim to include patients with HR-low and HER2-low disease who would usually be excluded from triple-negative breast cancer studies, but still have worse outcomes than HR-positive patients.

The second study, TROPION-Breast05, is evaluating dato-DXd alone and in combination with durvalumab in patients with locally recurrent inoperable or metastatic triple-negative breast cancer whose tumors express PD-L1 with a combined positive score (CPS) of 10 or higher.

In TROPION-Breast05, the researchers will compare the dato-DXd monotherapy and dato-DXd with durvalumab to investigator's choice of chemotherapy in combination with Keytruda. Researchers will enroll up to 625 patients in the trial.

The companies are also exploring dato-DXd monotherapy versus chemo in previously untreated locally recurrent, inoperable, or metastatic triple-negative breast cancer in another Phase III trial. There is also an ongoing Phase III trial of dato-DXd with or without durvalumab versus investigator's choice of therapy in patients with stage I to III triple-negative breast cancer with residual disease after neoadjuvant therapy.

Data from the TROPION-Breast01 Phase III trial of dato-DXd in advanced HR-positive, HER2-low or HER2-negative breast cancer showed that the treatment improved progression-free survival versus chemotherapy and that there was a trend toward improved overall survival on dato-DXd.