A targeted cancer therapy developed by AstraZeneca and Daiichi Sankyo has shown promising results in a Phase 3 study for advanced non-small cell lung cancer (NSCLC). The drug, called datopotamab deruxtecan, demonstrated a statistically significant improvement in progression-free survival compared to chemotherapy. However, the companies also disclosed that an unspecified number of patient deaths occurred during the study, which has raised concerns and clouded the preliminary results.
Datopotamab deruxtecan belongs to a class of therapies known as antibody drug conjugates (ADCs). It combines a targeting antibody, datopotamab, with a toxic drug payload, deruxtecan. The targeting ability of the antibody is designed to prevent the drug from harming healthy tissue. However, interstitial lung disease, characterized by scarring and inflammation in the lungs, has been observed as an adverse effect in clinical testing of similar ADCs developed by the partnership.
In the Phase 3 study, AstraZeneca and Daiichi Sankyo reported that interstitial lung disease occurred at mostly low grades and was consistent with previous trials. However, they also revealed that some grade 5 events, which are fatalities, were observed. No further details about the efficacy or safety of datopotamab deruxtecan have been released. The companies plan to present detailed results at an upcoming medical meeting and share them with regulators.
The goal of the study was to evaluate the therapy’s impact on both progression-free survival and overall survival. Overall survival data are not yet mature, so the trial will continue to assess this endpoint. The investigators and study participants will remain blinded to the results.
Datopotamab deruxtecan aims to provide a treatment option for NSCLC patients whose disease progresses after initial treatment with immunotherapy or targeted cancer therapies. Currently, the remaining treatment options for these patients are chemotherapy, which has limited efficacy and numerous side effects. No FDA-approved therapies target the protein TROP2, which the drug aims to target, for NSCLC. However, Gilead Sciences is conducting late-stage testing with an ADC called Trodelvy that targets TROP2.
AstraZeneca and Daiichi Sankyo began their ADC alliance in 2019, initially focused on a drug called Enhertu. They later partnered on developing datopotamab deruxtecan as a TROP2-targeting ADC for various solid tumors. AstraZeneca paid $1 billion upfront for the partnership, with an additional $5 billion tied to milestone achievements.
While the preliminary results of the Phase 3 study are promising, the disclosure of patient deaths raises concerns about the safety profile of datopotamab deruxtecan. Further analysis and investigation are needed to determine the extent and implications of these deaths. The companies remain committed to sharing the detailed results with regulators and discussing the next steps for the therapy.
