AstraZeneca's Datopotamab Deruxtecan Fails to Meet Overall Survival Endpoint in Phase 3 Breast Cancer Trial
Key Insights
AstraZeneca's datopotamab deruxtecan (Dato-DXd) did not achieve statistical significance in overall survival for breast cancer (search) patients in a Phase 3 trial.
The trial involved over 700 patients with inoperable or metastatic hormone receptor-positive, HER2 (search)-low or negative breast cancer (search).
AstraZeneca plans to submit the data to regulatory agencies, despite the uncertain regulatory future of Dato-DXd after these results.
AstraZeneca's shares experienced a decline following the announcement that its experimental drug, datopotamab deruxtecan (Dato-DXd), failed to meet the primary endpoint of overall survival in a Phase 3 trial for breast cancer (search). The trial involved over 700 patients with inoperable or metastatic hormone receptor-positive, HER2 (search)-low or negative breast cancer who had previously been treated with endocrine-based therapy and at least one systemic therapy. This setback follows closely on the heels of similar disappointing results from a lung cancer (search) trial involving the same drug.
Details of the Study
The Phase 3 trial compared Dato-DXd to standard chemotherapy in patients with advanced breast cancer (search). The primary endpoint was overall survival (OS), and the results indicated that Dato-DXd did not demonstrate a statistically significant improvement in OS compared to chemotherapy. AstraZeneca's Executive Vice President of Oncology R&D, Susan Galbraith, stated that the company believes that the results still show clinical value and will be shared with regulatory authorities.
Implications for Regulatory Approval
The failure to achieve statistical significance in overall survival raises concerns about the drug's potential for regulatory approval by the U.S. Food and Drug Administration (FDA). Analysts suggest that the absence of a clear OS benefit makes approval less likely. The FDA decision is anticipated in the first half of 2025. Datopotamab deruxtecan is being jointly developed with Japanese drugmaker Daiichi Sankyo.
Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan is an antibody-drug conjugate (ADC) that combines a tumor-seeking monoclonal antibody with a cell-killing chemotherapy payload. This targeted approach aims to deliver the cytotoxic agent directly to cancer cells, minimizing damage to healthy tissues. AstraZeneca and Daiichi Sankyo are also evaluating the drug alone and in combination with immunotherapy for the treatment of triple-negative or HR-low, HER2 (search)-negative breast cancers. While earlier trials showed some success in stalling cancer progression, these recent results have tempered expectations.