AstraZeneca and Daiichi Sankyo Narrow Lung Cancer Approval Strategy for Datopotamab Deruxtecan
Key Insights
AstraZeneca and Daiichi Sankyo have withdrawn their initial application for datopotamab deruxtecan (dato-dxd) in non-small cell lung cancer (search) (NSCLC).
A new application focuses on NSCLC patients with EGFR (search) mutations who have received prior systemic therapies, seeking accelerated approval.
This revised strategy follows discussions with U.S. regulators and mixed trial results, potentially limiting the drug's market.
AstraZeneca and Daiichi Sankyo have revised their regulatory strategy for datopotamab deruxtecan (dato-dxd), an antibody-drug conjugate, in non-small cell lung cancer (search) (NSCLC). The companies withdrew their initial broad application and are now pursuing accelerated approval for a narrower subset of NSCLC patients with epidermal growth factor receptor (EGFR (search)) mutations who have previously undergone systemic therapies. This decision follows discussions with the U.S. Food and Drug Administration (FDA) and analysis of clinical trial data.
The initial application for dato-dxd targeted patients with NSCLC whose tumors express the TROP2 (search) protein. However, a Phase 3 study comparing dato-dxd to docetaxel chemotherapy did not show a significant overall survival benefit. Subsequent data presented in September further complicated the picture, as dato-dxd failed to demonstrate a meaningful survival extension even in the nonsquamous subgroup.
Revised Strategy Focuses on EGFR-Mutated NSCLC
The revised strategy hinges on a pooled analysis of data from two clinical trials, focusing specifically on patients with previously treated, EGFR (search)-mutated NSCLC. According to AstraZeneca, these findings demonstrated a “pronounced benefit” in this patient population, which informed discussions with the FDA. EGFR mutations are estimated to be present in 10% to 15% of NSCLC cases in the U.S. and Europe, and approximately 30% to 40% in Asia.
Susan Galbraith, AstraZeneca’s head of oncology R&D, stated that the data in EGFR (search)-mutated patients "showed an especially pronounced benefit," which drove the decision to engage with the FDA.
Implications and Ongoing Studies
Analysts view this strategic shift as a setback, albeit one that mitigates the risk of outright rejection. Jefferies analyst Peter Welford noted that the new approach “removes the risk” of a complete rejection. Dato-dxd is also being evaluated in combination with AstraZeneca's Tagrisso in Phase 3 trials for EGFR (search)-mutated, nonsquamous NSCLC. Additionally, the drug is under FDA review for breast cancer (search), with a decision expected in early 2025.
Datopotamab deruxtecan is designed to target TROP2 (search), a protein overexpressed in many lung cancers. It is one of several antibody-drug conjugates being developed by AstraZeneca and Daiichi Sankyo with the goal of replacing chemotherapy in various tumor types. Their first such drug, Enhertu, has already transformed the treatment landscape for certain breast cancers.