High-level overall survival (OS) results from the TROPION-Lung01 Phase III trial, which previously met the primary endpoint of progression-free survival (PFS), numerically favored datopotamab deruxtecan (Dato-DXd) over docetaxel in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with at least one prior line of therapy. Although survival results did not reach statistical significance in the overall trial population, the prespecified subgroup of patients with nonsquamous NSCLC showed a clinically meaningful improvement in OS with datopotamab deruxtecan compared to docetaxel.
The final OS analysis builds on the positive PFS results presented at the 2023 European Society for Medical Oncology Congress, which showed a statistically significant improvement in PFS in the overall trial population and a clinically meaningful PFS benefit in patients with nonsquamous NSCLC. Patient enrollment by tumor histology was balanced across treatment arms, with approximately 75% of patients having nonsquamous NSCLC.
Datopotamab deruxtecan’s safety profile in TROPION-Lung01 was consistent with previous analyses, showing fewer dose reductions or discontinuations due to adverse events compared to docetaxel, and no new safety concerns were identified. No new interstitial lung disease events were adjudicated as drug-related.
Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, stated that datopotamab deruxtecan is the only investigational therapy to show a clinically meaningful survival improvement in previously treated nonsquamous NSCLC patients compared to docetaxel. Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo, added that the survival improvement, coupled with the significant PFS benefit, suggests that this TROP2-directed antibody drug conjugate could become an important new treatment for nonsquamous NSCLC in the advanced setting.
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate developed by Daiichi Sankyo and jointly developed with AstraZeneca. The data will be presented at a forthcoming medical meeting and support regulatory applications currently under review globally, including in the US and EU.
Notes:
- Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 80% of cases. Around 75% of NSCLC tumors are nonsquamous.
- TROPION-Lung01 is a global, randomized, multicenter, open-label Phase III trial evaluating datopotamab deruxtecan versus docetaxel in adult patients with locally advanced or metastatic NSCLC.
- The trial’s primary endpoints are PFS and OS, with key secondary endpoints including objective response rate and safety.
- Datopotamab deruxtecan (Dato-DXd) is part of a comprehensive global clinical development program evaluating its efficacy and safety across multiple cancers.
- AstraZeneca and Daiichi Sankyo have a global collaboration to jointly develop and commercialize Enhertu and datopotamab deruxtecan.
AstraZeneca is focused on improving lung cancer outcomes through early detection and innovative treatments, aiming to transform cancer care and eliminate cancer as a cause of death.
