NEW YORK – In the Phase III TROPION-Breast01 clinical trial, patients with previously treated hormone receptor (HR)-positive, HER2-negative or -low breast cancer did not experience a statistically significant overall survival benefit from datopotamab deruxtecan (Dato-DXd) compared to chemotherapy, a finding that AstraZeneca and Daiichi Sankyo will share with regulators.
Despite the miss, in a statement on Monday, the companies expressed hope that the totality of evidence on Dato-DXd in this setting, including its ability to improve progression-free survival compared to chemo, will convince regulators of its benefit.
AstraZeneca and Daiichi Sankyo, which are jointly developing the TROP2-directed antibody-drug conjugate, filed a biologics licensing application with the US Food and Drug Administration seeking approval for Dato-DXd as a treatment for HR-positive, HER2-negative or -low breast cancer, a subset defined as those with immunohistochemistry scores of 0, 1+, or 2+ and in situ hybridization negative. The agency is expected to decide whether to approve Dato-DXd in this setting in the first quarter of 2025. In addition to having better median progression-free survival on Dato-DXd, patients on the antibody-drug conjugate also reported better outcomes compared to those on chemo, AstraZeneca and Daiichi Sankyo highlighted in a statement.
The companies also pointed to the changed landscape for metastatic HR-positive breast cancer as a potential reason why TROPION-Breast01 failed to meet the overall survival endpoint. After study participants experienced disease progression or discontinued treatment, they could go on to receive other effective treatments, including another AstraZeneca/Daiichi Sankyo antibody-drug conjugate, Enhertu (trastuzumab deruxtecan). This subsequent therapy could have muddied the long-term overall survival analysis between Dato-DXd and chemo arms.
"The metastatic HR-positive breast cancer treatment landscape has advanced remarkably in the last several years to the benefit of patients," Susan Galbraith, the executive VP of oncology R&D at AstraZeneca, said in a statement. "Based on the TROPION-Breast01 results, there is evidence of the clinical value of datopotamab deruxtecan in this setting. We will continue discussions with regulatory authorities and apply insights from these results to our clinical development program for datopotamab deruxtecan in breast cancer."
AstraZeneca and Daiichi Sankyo will present the full results from TROPION-Breast01 at an upcoming medical meeting.
The partners are also evaluating Dato-DXd as a monotherapy and in combination with immunotherapy in patients with triple-negative breast cancer or HR-low, HER2-negative breast cancer.