On July 3, 2023, AstraZeneca presented encouraging top-line results from the TROPION-Lung01 Phase III trial that demonstrated the positive efficacy of datopotamab deruxtecan (Dato-DXd) compared to docetaxel, the standard chemotherapy, in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The trial focused on patients who had received at least one prior therapy.
The trial successfully met its dual primary endpoint of progression-free survival (PFS), showing a significant improvement with datopotamab deruxtecan compared to docetaxel. However, for the dual primary endpoint of overall survival (OS), the data were not yet mature at the time of the interim analysis. While an early trend in favor of datopotamab deruxtecan was observed, it did not reach the predetermined threshold for statistical significance. The trial will continue to assess OS as planned, with further data needed for a conclusive evaluation. Blinding of the investigators and participants will be maintained.
“With TROPION-Lung01, we met the dual primary endpoint of progression-free survival, challenging the entrenched standard of care in a previously treated and unselected patient population that has long deserved an alternative to chemotherapy. These first Phase III trial results from the datopotamab deruxtecan clinical programme provide compelling evidence for the potential role this TROP2-directed antibody drug conjugate can play in treating patients with lung cancer.”
– Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca
The safety profile of datopotamab deruxtecan remained consistent with previous clinical trials, with no new safety concerns identified. Cases of all-grade interstitial lung disease were generally in line with earlier trials, predominantly presenting as low-grade. However, some Grade 5 events were observed.
“We are encouraged by the statistically significant results of the dual primary endpoint of progression-free survival seen with datopotamab deruxtecan and look forward to the final overall survival analysis. We plan to share these data with regulatory authorities to discuss next steps.”
– Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo
Datopotamab deruxtecan is a targeted antibody drug conjugate (ADC) designed to specifically act on TROP2, developed jointly by AstraZeneca and Daiichi Sankyo. The trial included patients with and without actionable genomic alterations, such as EGFR and ALK. Those with actionable genomic alterations had previously received platinum-based chemotherapy and approved targeted therapies, while patients without such alterations had undergone platinum-based chemotherapy along with a PD-1 or PD-L1 inhibitor, either concurrently or sequentially.
The detailed findings of the trial will be presented at an upcoming medical meeting and shared with relevant health authorities for further evaluation.
