AstraZeneca’s antibody drug conjugate datopotamab deruxtecan (Dato-DXd) has shown a statistically significant improvement for the dual primary end-point of progression-free survival (PFS) in patients with advanced or metastatic non-small cell lung cancer (NSCLC) compared to the current standard-of-care treatment docetaxel, the company announced on Wednesday.
The company also noted that the data from the TROPION-Lung01 trial were not mature enough for the dual primary endpoint of overall survival (OS) of the candidate versus docetaxel to meet the prespecified threshold for statistical significance, but the trial would continue as planned to assess OS with greater maturity.
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.
“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,” said Susan Galbraith, executive vice resident, Oncology R&D at AstraZeneca. “These first Phase III trial results from the datopotamab deruxtecan clinical program provide compelling evidence for the potential role this TROP2-directed antibody drug conjugate can play in treating patients with lung cancer.”
The company noted that the safety profile of datopotamab deruxtecan was consistent with previous trials and that no new safety signals were found. All grade interstitial lung disease was also generally consistent with prior clinical trials, with the majority being low grade, though some Grade 5 events were observed.
The TROPION-Lung01 study enrolled patients with and without actionable genomic alterations, such as EGFR and ALK. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.
Datopotamab deruxtecan has the potential to become a treatment alternative for patients with advanced or metastatic NSCLC. While there have been significant improvements in first-line therapies for NSCLC such as immunotherapies and other targeted treatments, most patients will progress and eventually receive chemotherapy as the last line of defense due to the lack of other effective methods of treating the disease. This despite the fact that chemotherapy has significant side effects and is only marginally effective. The TROP2 protein is highly expressed in a majority of cancers and there are currently no TROP2-directed antibody drug conjugates for the treatment of lung cancer.